Decades-old laws barring foreign ownership of farmland in Iowa, Missouri and at least three other Midwest states may complicate Chinese company Shuanghui International's $4.7 billion planned purchase of U.S. pork powerhouse Smithfield Foods.
The deal, which would be the biggest purchase in the United States by a Chinese company, will face scrutiny from a federal government panel that assesses national security risks, but that is not expected to block the sale.
A few politicians have raised concerns about food safety, and farmers groups have expressed worries about consolidation and potential damage to small farmers. The land laws could be invoked by those opposed to the deal, and at the very least may require some complex legal maneuvering by the companies.
The statutes in question, some first adopted during the 1970s in response to fast-paced Japanese investment in U.S. real estate, restrict foreign businesses or governments from owning or controlling U.S. land used for livestock or crop production. The laws could provide Midwestern states legal recourse against the Smithfield deal.
At least eight states - Iowa, Nebraska, Minnesota, Missouri, North Dakota, Oklahoma, South Dakota and Wisconsin - have laws that prohibit foreign ownership of agricultural land. If the Shuanghui acquisition goes through, any hog farms, crop fields, manure lagoons or other land used for agricultural production and now owned by Smithfield in these states, could invite legal challenges.
Smithfield's 11 slaughterhouses and meat factories in the eight states likely are exempt, legal experts said. However, some of those operations may rely on farm, feed or waste facilities that could be subject to legal challenge.
Smithfield does not disclose specifics of its property holdings, and the company declined to comment for this story. But a source close to the deal told Reuters that dealmakers and lawyers were aware of the issues, and the foreign ownership laws in different U.S. states had been discussed leading up to the May 29 deal announcement.
They believe the laws will not jeopardize Shuanghui's ability to close its purchase as planned in the second half of this year. However, the restrictions could affect how Smithfield and its subsidiaries operate post-merger, the source added.
The morning the deal was announced, Smithfield's attorneys sent a letter to Iowa Attorney General Tom Miller's office, alerting the agency to the takeover. Since then, in Iowa and elsewhere, state officials, legal experts and industry critics are raising questions about whether Smithfield under Shuanghui ownership will comply with these little-known and rarely tested laws, Reuters has learned.
In Iowa, Miller's office is seeking more information from Smithfield about the deal, a spokesman said.
The nation's largest hog producing state and its Democrat Attorney General have a history of opposing Smithfield's corporate transactions. The company currently operates in Iowa under a consent decree with Miller, who had charged that a 2000 acquisition by Virginia-based Smithfield violated a state law barring livestock production by meat packers.
The letter Smithfield sent declared that the merger will not change its current agreements or commitments with the state ? a possible reference to the consent decree.
Any state that does seek to challenge the Smithfield deal could find itself attempting to unravel a snarl of property ownership records.
"It's hard to police because you start getting layers of entities and you've got to figure out who owns what and where they are exactly," said Anthony Schutz, an associate professor at the University of Nebraska College of Law in Lincoln.
Smithfield's publicly available corporate records do not disclose how much farmland Smithfield and its subsidiaries own in states with laws barring foreign ownership.
Smithfield's Murphy-Brown of Missouri owns farmland in that state, according to court filings and tax records. Its Murphy-Brown West division operates 150 company-owned farms in eight states: Illinois, Iowa, Missouri, Oklahoma, South Dakota, Texas, Utah and Colorado.
Three of those states have laws against foreign ownership, though a pending change to Missouri law could ease the way for foreign owners. But even in the states with such laws, companies have succeeded in finding ways to elude such restrictions, say legal experts.
In Iowa, for example, entities can create a U.S. subsidiary that is more than 50 percent controlled by people who meet the residency requirements, said Roger McEowen, director of the Iowa State University's Center for Agricultural Law and Taxation.
A Chinese market hungry for grains and meats has generally been embraced by the Midwest farm economy, but subtle rifts are beginning to show between farmers who stand to benefit from a boost in pork production after the takeover and those who won't.
Farmers like Chris Petersen of Clear Lake, Iowa, are concerned. A hog producer whose family has farmed in the Midwest for generations, Petersen said he was taken aback by comments made by Chinese investors and Smithfield officials last year at a closed-door symposium he attended. "All they could talk about was how much pork they were going to sell and how much money they were going to make," Petersen said.
JERUSALEM (Reuters) - Prime Minister Benjamin Netanyahu hinted on Monday that Israel was ready to confine Jewish settlement expansion to the blocs of occupied territory it wants to keep under any peace deal with the Palestinians, in a nod to U.S. efforts to revive stalled negotiations.
Settlement construction was cited as a key reason for the breakdown of U.S.-sponsored peace talks in 2010, and a stumbling block to Secretary of State John Kerry's latest efforts to revive negotiations towards founding a Palestinian state in land Israel captured in the 1967 Middle East war.
Netanyahu told Parliament's Foreign Affairs and Defense Committee that he wanted to resume peace talks, but that construction in the settlements in the West Bank would continue, "and continues today".
He added, though, that "we have to be smart about it, not just correct".
"Settlement in the blocs wouldn't substantively change the ability to reach an agreement," he said, referring to several clusters of enclaves where a majority of settlers live.
Netanyahu spoke behind closed doors and officials released some of his remarks in a statement issued later to reporters.
Israel has long said that under any peace agreement it intends to keep its largest settler enclaves built in Ariel, near the Palestinian city of Nablus, in Gush Etzion in the Bethlehem area, and in the Jerusalem area.
Palestinian President Mahmoud Abbas has so far linked a resumption of peace talks to a total freeze in settlement construction, which Palestinians see as establishing facts on the ground that deny them land they need for a viable state.
One of Netanyahu's senior political partners, member of parliament Avigdor Lieberman, told Army Radio Israel was already observing a break in construction in East Jerusalem.
"One should view this as a temporary hiatus," the former foreign minister said. He added: "We have an interest in Kerry succeeding."
Israel captured East Jerusalem in the same war in which it took the West Bank, but annexed the city as part of its capital in a move never recognized internationally. Palestinians want East Jerusalem to be capital of their future state.
Since taking office in February, Kerry has visited Israel and the Palestinian territories four times in his drive to win the agreement of the sides to renew negotiations.
(Writing by Allyn Fisher-Ilan; Editing by Mark Trevelyan)
We all know the benefits of writing and submitting articles online. Your business and website benefits by providing useful information that your readers find helpful, and in turn, you increase your reputation as a reliable source of information in your niche. This leads to more sales, more hits on your website, and a gradual increase in overall traffic. But there is something else that article marketing can bring you that other forms of online advertising lack: trust.
Trust is an essential part of any supplier-consumer relationship; if I can't trust you to deliver a product that will work, why would I choose to do business with you? When it comes to online business, this trust is even more important: without a face-to-face interaction, you are relying on your online reputation to bring in business.
This is where article marketing comes in. By showing your readers you know what you're talking about, you can develop a level of trust that simply isn't possible with fleeting side-screen ads and other online delivery systems.
So how can you make the most of this opportunity? Here are some article marketing tips for using your articles to build trust with your readers:
1. Be Consistent
By consistently creating and distributing articles, you can show you have a lot to say about your niche, and that you're a dependable source of information.
When you've got a whole heap of articles about your niche and keep producing more, this tells customers that you are here to stay: a fixture in your area of expertise, you can easily be relied upon.
2. Teach Your Readers
Not only is teaching one of the easiest ways to produce a lot of articles easily, but it means readers looking for information in your niche will turn to you for the answers they need. If your readers can rely on you for dependable information, then that is a good sign they can rely on you for other related services.
Make sure you provide unique information, in order to stand out from the crowd. By giving your readers something they can't find elsewhere - a new perspective on frequently-discussed topics, for example - you'll come across as the expert in your field, and will more likely be seen as the authority readers would trust in a given niche.
3. Be Idiosyncratic
Idiosyncratic is a big word for something really small: the uniqueness of your voice. Everyone has their own way of speaking, their own style of delivery, and it's translated onto paper (or Word document!) when you write. Instead of seeing your articles as just throwaway submissions, try and look at them as your chance to communicate directly with potential customers. Let your style and personality shine through, and you'll stand out from the crowd as more than just an encyclopedia.
Remember that both you and your readers are real human beings - so don't try to sound like a computer! Share your experiences, thoughts, and even successes and failures, in order to create an emotional connection with your readers that will keep them coming back for more of your genuine, heartfelt advice.
4. Encourage Your Readers
If you're teaching through articles, chances are that the vast majority of your readers will be beginners who are just starting out - those are the people that are most likely to turn to the internet for advice. However, being a novice can be a frustrating experience, especially if you're already good at other things, and feel that your new skill is somewhat below par.
Empathize with your readers on this point, and encourage them to keep going. By showing them you know what it feels like to be in their position, they are far more likely to stick to their learning - and to be grateful to you for helping them through your empathy and encouragement.
5. Speak Plainly
It's always tempting to write in elaborate sentences and big fancy words - but most people will find this to be a turn-off. Avoid industry jargon and complex terms, and instead stick to plain, simple English that everyone can get on board with. If you have to use an abbreviation or technical term, make sure you explain it in a way that everybody understands - that way, nobody will feel left out, and your readers will appreciate you making the effort to communicate with them in a way they understand.
You'll notice some common themes in this advice I'm giving:
Be yourself, write in your own voice, teach, encourage, and write in plain English. As you're getting started, focus on just a few of these at a time. Writing is an art form and a skill - you will get better at accomplishing these points the more articles you write.
Author Resource:- Steve Shaw's article distribution service has helped thousands of business owners worldwide build traffic, leads and sales to their websites. Submit your article to 100 top article directories for just $2 - go now to http://www.submityourarticle.com
Article From Article Cupboard Free Article Directory
Related Articles
HTML Ready Article. Click on the "Copy" button to copy into your clipboard.
By: Steve Shaw
We all know the benefits of writing and submitting articles online. Your business and website benefits by providing useful information that your readers find helpful, and in turn, you increase your reputation as a reliable source of information in your niche. This leads to more sales, more hits on your website, and a gradual increase in overall traffic. But there is something else that article marketing can bring you that other forms of online advertising lack: trust.
Trust is an essential part of any supplier-consumer relationship; if I can't trust you to deliver a product that will work, why would I choose to do business with you? When it comes to online business, this trust is even more important: without a face-to-face interaction, you are relying on your online reputation to bring in business.
This is where article marketing comes in. By showing your readers you know what you're talking about, you can develop a level of trust that simply isn't possible with fleeting side-screen ads and other online delivery systems.
So how can you make the most of this opportunity? Here are some article marketing tips for using your articles to build trust with your readers:
1. Be Consistent
By consistently creating and distributing articles, you can show you have a lot to say about your niche, and that you're a dependable source of information.
When you've got a whole heap of articles about your niche and keep producing more, this tells customers that you are here to stay: a fixture in your area of expertise, you can easily be relied upon.
2. Teach Your Readers
Not only is teaching one of the easiest ways to produce a lot of articles easily, but it means readers looking for information in your niche will turn to you for the answers they need. If your readers can rely on you for dependable information, then that is a good sign they can rely on you for other related services.
Make sure you provide unique information, in order to stand out from the crowd. By giving your readers something they can't find elsewhere - a new perspective on frequently-discussed topics, for example - you'll come across as the expert in your field, and will more likely be seen as the authority readers would trust in a given niche.
3. Be Idiosyncratic
Idiosyncratic is a big word for something really small: the uniqueness of your voice. Everyone has their own way of speaking, their own style of delivery, and it's translated onto paper (or Word document!) when you write. Instead of seeing your articles as just throwaway submissions, try and look at them as your chance to communicate directly with potential customers. Let your style and personality shine through, and you'll stand out from the crowd as more than just an encyclopedia.
Remember that both you and your readers are real human beings - so don't try to sound like a computer! Share your experiences, thoughts, and even successes and failures, in order to create an emotional connection with your readers that will keep them coming back for more of your genuine, heartfelt advice.
4. Encourage Your Readers
If you're teaching through articles, chances are that the vast majority of your readers will be beginners who are just starting out - those are the people that are most likely to turn to the internet for advice. However, being a novice can be a frustrating experience, especially if you're already good at other things, and feel that your new skill is somewhat below par.
Empathize with your readers on this point, and encourage them to keep going. By showing them you know what it feels like to be in their position, they are far more likely to stick to their learning - and to be grateful to you for helping them through your empathy and encouragement.
5. Speak Plainly
It's always tempting to write in elaborate sentences and big fancy words - but most people will find this to be a turn-off. Avoid industry jargon and complex terms, and instead stick to plain, simple English that everyone can get on board with. If you have to use an abbreviation or technical term, make sure you explain it in a way that everybody understands - that way, nobody will feel left out, and your readers will appreciate you making the effort to communicate with them in a way they understand.
You'll notice some common themes in this advice I'm giving:
Be yourself, write in your own voice, teach, encourage, and write in plain English. As you're getting started, focus on just a few of these at a time. Writing is an art form and a skill - you will get better at accomplishing these points the more articles you write.
Author Resource:->??Steve Shaw's article distribution service has helped thousands of business owners worldwide build traffic, leads and sales to their websites. Submit your article to 100 top article directories for just $2 - go now to http://www.submityourarticle.com
Article From Article Cupboard Free Article Directory
CAIRO (Reuters) - Egypt's foreign minister, vowing not to give up "a single drop of water from the Nile", said on Sunday he would go to Addis Ababa to discuss a giant dam that Ethiopia has begun building in defiance of Cairo's objections.
Speaking to Egypt's state news agency MENA two days after the Ethiopian government flatly rejected a request from Cairo to halt the project, Mohamed Kamel Amr said Egyptians view any obstacle to the river's flow as a threat to national survival.
"No Nile - no Egypt," he said, highlighting the pressure on the Egyptian government, whose popularity is wilting in the face of economic troubles, to prevent the hydro power plant cutting already stretched water supplies for its 84 million people.
Last week, Ethiopia summoned the Egyptian ambassador after politicians in Cairo were shown on television suggesting military action or supporting Ethiopian rebels - a mark of the threat felt in Cairo from the plan to dam the Blue Nile, the tributary that supplies the bulk of water downstream in Egypt.
"Egypt won't give up on a single drop of water from the Nile or any part of what arrives into Egypt from this water in terms of quantity and quality," Amr told MENA, noting that Egypt has little rain and is effectively desert without its great river.
Speaking at a news conference, he declined to detail the action Egypt might take next but noted Ethiopian assurances that Africa's biggest hydro station would not cut water supplies.
"We have a plan for action, which will start soon," Amr said. "We'll talk to Ethiopia and we'll see what comes of it.
"Ethiopia has said it will not harm Egypt, not even by a liter of water. We are looking at ... this being implemented."
Countries that share the Nile have long argued over the use of its waters, repeatedly raising fears that the disputes could eventually boil over into war. Egypt, struggling with a shortage of cash and bitter internal political divisions following a 2011 revolution, called on Ethiopia to stop work after engineers began diverting the course of the Blue Nile late last month.
In Addis Ababa, a government spokesman called that request a "non-starter" and dismissed threats from Cairo of "sabotage" and "destabilization", saying attempts by Egypt under its previous military rulers to undermine Ethiopian leaders had failed.
The possible downstream effects of the $4.7-billion Grand Renaissance Dam, some 40 km (25 miles) from Ethiopia's border with Sudan, have been disputed and full details are unclear.
While letting water through such dams - of which Egypt, Sudan and Ethiopia already have several - may not reduce its flow greatly, the filling of the reservoir behind any new dam means cutting the river's flow for a time. Evaporation from reservoirs can also permanently reduce water flowing downstream.
Now 21 percent complete, the new dam on the Blue Nile will eventually have capacity of 6,000 megawatts and is central to Ethiopia's plans to become Africa's leading exporter of power.
Sudan, which borders Egypt and Ethiopia and also gets much of its water from the Nile, said it supported the project.
"The Grand Renaissance Dam brings many benefits and blessings for us," Information Minister Ahmed Belal Osman told reporters in Khartoum.
He gave no details, but Sudanese officials have said the dam will enable Ethiopia to export power to Sudan, a country with frequent outages and one of its closest allies in Africa.
(Editing by Alastair Macdonald, Tom Pfeiffer and Kevin Liffey)
When calculating cell-growth thermodynamics, reconsider using the Gibbs free energy equationPublic release date: 10-Jun-2013 [ | E-mail | Share ]
Contact: Emily Murphy emurphy@press.uchicago.edu 773-702-7521 University of Chicago Press Journals
A forthcoming article in The Quarterly Review of Biology provides the basis for an argument against using the Gibbs free energy equation to accurately determine the thermodynamics of microbial growth.
Microbial growth is a biological process that has been previously treated as a chemical reaction operating in accord with the Gibbs free energy equation, developed during the 1870s. The heat of yeast growth was the first to be measured by direct calorimetry, in 1856. However, the full application of the Gibbs equation to microbial growth did not occur until 1997, with the experimental measurement of yeast cell entropy. Subsequent investigations showed that the quantity of absorbed thermal energy for solid substances had two values, depending on how it was calculated. Because there can be only one correct value at a given temperature, Dr. Edwin H. Battley, emeritus of Stony Brook University and recipient of the International Society for Biological Calorimetry's Dubrunfaut Award (1994) and Lavoisier Medal (2010), examined the use of the Gibbs free energy equation to accurately determine the change in energy that accompanies cellular growth.
In many systems, the values for some variables cannot be determined experimentally and so must be calculated from theoretically derived values. The free energy change accompanying cellular growth cannot be directly measured but, if the heat of growth can be measured and the entropy change accompanying growth can be calculated indirectly from heat measurements, the free energy change can be calculated using the Gibbs free energy equation.
The basis for Battley's review is in the observation of an apparent discrepancy between the amounts of growth obtained when S. cerevisiae was grown on glucose in aerobic or anaerobic conditions. Assuming it is the change in the Gibbs energy that drives the reactions that occur in both conditions, it is expected that the amount of growth would be proportional to the amount of nonthermal energy initially available and there would be 13.2 times more growth aerobically than anaerobically. However, when the growth for these two systems was measured turbidometrically, this value was found to be only 3.4. It is clear that a discrepancy exists between what is theoretically expected and what is experimentally determined.
Using results of earlier studies, Battley devised a different equation to calculate the thermodynamics of microbial growth. This involves using a different mathematical procedure to calculate enthalpy values for absorbed thermal energy exchange. As a consequence, values for entropy used for this purpose are removed. He found that the application of this equation (which he calls the Battley free energy equation) achieved values different from those obtained using the Gibbs free energy equation for the same system. Because the Battley free energy equation uses an absorbed thermal energy variable that is easier to understand in the context of the real-world system in which microbes exist, Battley argues that his free energy equation more realistically represents real-world conditions, and in a way that is more simple and parsimonious to calculate. As such, it is superior for determining the thermodynamics of microbial growth than is the Gibbs free energy equation.
###
Battley, Edwin H. "A Theoretical Study of the Thermodynamics of Microbial Growth Using Saccharomyces cerevisiae and a Different Free Energy Equation." Quarterly Review of Biology Vol. 88, No. 2 (June 2013).
The Quarterly Review of Biology, the premier review journal in biology, has presented insightful historical, philosophical, and technical treatments of important biological topics since 1926. The QRB publishes outstanding review articles of generous length that are guided by an expansive, inclusive, and often humanistic understanding of biology. Beyond the core biological sciences, the QRB is also an important review journal for scholars in related areas, including policy studies and the history and philosophy of science.
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
When calculating cell-growth thermodynamics, reconsider using the Gibbs free energy equationPublic release date: 10-Jun-2013 [ | E-mail | Share ]
Contact: Emily Murphy emurphy@press.uchicago.edu 773-702-7521 University of Chicago Press Journals
A forthcoming article in The Quarterly Review of Biology provides the basis for an argument against using the Gibbs free energy equation to accurately determine the thermodynamics of microbial growth.
Microbial growth is a biological process that has been previously treated as a chemical reaction operating in accord with the Gibbs free energy equation, developed during the 1870s. The heat of yeast growth was the first to be measured by direct calorimetry, in 1856. However, the full application of the Gibbs equation to microbial growth did not occur until 1997, with the experimental measurement of yeast cell entropy. Subsequent investigations showed that the quantity of absorbed thermal energy for solid substances had two values, depending on how it was calculated. Because there can be only one correct value at a given temperature, Dr. Edwin H. Battley, emeritus of Stony Brook University and recipient of the International Society for Biological Calorimetry's Dubrunfaut Award (1994) and Lavoisier Medal (2010), examined the use of the Gibbs free energy equation to accurately determine the change in energy that accompanies cellular growth.
In many systems, the values for some variables cannot be determined experimentally and so must be calculated from theoretically derived values. The free energy change accompanying cellular growth cannot be directly measured but, if the heat of growth can be measured and the entropy change accompanying growth can be calculated indirectly from heat measurements, the free energy change can be calculated using the Gibbs free energy equation.
The basis for Battley's review is in the observation of an apparent discrepancy between the amounts of growth obtained when S. cerevisiae was grown on glucose in aerobic or anaerobic conditions. Assuming it is the change in the Gibbs energy that drives the reactions that occur in both conditions, it is expected that the amount of growth would be proportional to the amount of nonthermal energy initially available and there would be 13.2 times more growth aerobically than anaerobically. However, when the growth for these two systems was measured turbidometrically, this value was found to be only 3.4. It is clear that a discrepancy exists between what is theoretically expected and what is experimentally determined.
Using results of earlier studies, Battley devised a different equation to calculate the thermodynamics of microbial growth. This involves using a different mathematical procedure to calculate enthalpy values for absorbed thermal energy exchange. As a consequence, values for entropy used for this purpose are removed. He found that the application of this equation (which he calls the Battley free energy equation) achieved values different from those obtained using the Gibbs free energy equation for the same system. Because the Battley free energy equation uses an absorbed thermal energy variable that is easier to understand in the context of the real-world system in which microbes exist, Battley argues that his free energy equation more realistically represents real-world conditions, and in a way that is more simple and parsimonious to calculate. As such, it is superior for determining the thermodynamics of microbial growth than is the Gibbs free energy equation.
###
Battley, Edwin H. "A Theoretical Study of the Thermodynamics of Microbial Growth Using Saccharomyces cerevisiae and a Different Free Energy Equation." Quarterly Review of Biology Vol. 88, No. 2 (June 2013).
The Quarterly Review of Biology, the premier review journal in biology, has presented insightful historical, philosophical, and technical treatments of important biological topics since 1926. The QRB publishes outstanding review articles of generous length that are guided by an expansive, inclusive, and often humanistic understanding of biology. Beyond the core biological sciences, the QRB is also an important review journal for scholars in related areas, including policy studies and the history and philosophy of science.
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
When oxygen is short, EGFR prevents maturation of cancer-fighting miRNAsPublic release date: 23-May-2013 [ | E-mail | Share ]
Contact: Scott Merville smerville@mdanderson.org 713-792-0661 University of Texas M. D. Anderson Cancer Center
With tumor suppressors frozen in adolescence, resistant cancer cells cheat death
HOUSTON - Even while being dragged to its destruction inside a cell, a cancer-promoting growth factor receptor fires away, sending signals that thwart the development of tumor-suppressing microRNAs (miRNAs) before it's dissolved, researchers reported in an early online publication at Nature.
Under conditions of oxygen starvation often encountered by tumors, the epidermal growth factor receptor (EGFR) gums up the cell's miRNA-processing machinery, an international team led by scientists at The University of Texas MD Anderson Cancer Center discovered.
"So when hypoxia stresses a cell, signaling by EGFR prevents immature miRNAs from growing up to fight cancer," said senior author Mien-Chie Hung, Ph.D., professor and chair of MD Anderson's Department of Molecular and Cellular Oncology and holder of the Ruth Legett Jones Distinguished Chair.
The group's findings point to a potential new prognostic marker for breast cancer, Hung noted, but also provide the first evidence of a growth factor signaling pathway regulating miRNA maturation.
"Inside of a cell, you have signal induction, in this case through EGFR, and you also have a protein complex that processes precursors into mature miRNA to perform a function. They didn't appear to talk to each other, it's as if one speaks English and the other Chinese," Hung said. "This is the first paper to show how they communicate."
The scientists established the relationship in cell line experiments, confirmed it in a mouse model and human breast cancer samples, then found that it reduced breast cancer patient survival in a review of 125 cases.
A new cancer-promoting role identified for EGFR
EGFR penetrates the cell membrane to receive signals from growth factors outside of the cell. After a growth factor binds to it, EGFR conveys the signal into the cell by attaching phosphate groups to other proteins, often acting as a molecular "on switch."
In many cancers, EGFR is overexpressed or dysfunctional, constantly sending signals to cells to divide. Hung and colleagues found that EGFR also fuels cancer progression by stifling tumor-suppressing miRNAs.
As a tumor grows, large portions of its interior can become starved for oxygen (hypoxia) for lack of adequate blood vessels. This stress suffocates many tumor cells, but the few that endure become highly malignant, resist treatment and are most likely to spread, Hung said.
Anti-angiogenesis drugs designed to kill tumors by blocking their ability to spin webs of supportive blood vessels often succeed at first, Hung said, but then fail against the more malignant cells that survive hypoxia.
When hypoxia hits, EGFR gets active and gets eaten
Low-oxygen conditions cause EGFR overexpression. EGFR also is pulled into the cell interior, captured in cavities called vesicles and eventually fed into lysosomes, a membrane-enclosed organelle loaded with enzymes to dissolve proteins.
It was known that EGFR continues to signal even while caught in the vesicles, which actually prolongs its activation. Hung and colleagues found that EGFR signals to a key protein in miRNA processing called argonaute 2, or AGO2.
AGO2 connects with two other proteins called Dicer and TRBP to form a complex that processes microRNA precursors into mature miRNAs, which regulate gene expression after messenger RNA has been expressed but before it's translated into a protein.
Oncoprotein-regulating miRNAs don't grow up
The scientists found that EGFR attaches phosphate groups to AGO2, which in turn weakens AGO2's ability to connect with Dicer to produce mature microRNAs. EGFR's effect is stronger during oxygen starvation than under normal conditions.
The team identified a number of specific miRNAs affected by EGFR, most of which have been reported to have tumor suppressor characteristics. The miRNAs regulated by phosphorylated AGO2, including miR-31, miR-192 and miR-193a-5p, also shared a long-loop structure in their precursors that miRNAs unaffected by AGO2 phosphorylation lack.
Hypoxic environments around tumors promote metastasis by helping cells evade programmed cell death. Hung and colleagues showed that EGFR-mediated AGO2 phosphorylation blocks cell death and enhances invasiveness under hypoxia.
Experiments in a mouse model of breast cancer confirmed that expression of EGFR and the presence of phosphorylated AGO2 increase during tumor progression under oxygen-starved conditions.
EGFR-AGO2 connection found in human breast tumors; reduces survival
The hypoxia-EGFR-AGO2 connection was strong in tumor samples from 128 breast cancer patients, but it was low or absent in normal breast tissue. In 125 breast cancer cases analyzed by the team, half of 62 patients with high levels of phosphorylated AGO2 survived to 48 months and beyond. Median survival had not been reached for the 63 patients in the low-level group, but 78 percent had survived to 48 months.
"One can imagine other receptors for platelet-derived growth factor and insulin-like growth factor also regulating miRNAs, perhaps by regulating Dicer or TBRP," Hung said. "This is a turning-point paper; it will induce lots of new questions for scientists to pursue."
###
Co-authors with Hung are lead author Jia Shen, Weiya Xia, M.D., Yekaterina Khotskaya, Ph.D., Longfei Huo, Ph.D., Seung-Oe Lim, Ph.D., Yi Du, Ph.D., Yan Wang, Ph.D., Jennifer Hsu, Ph.D., and Yung Carmen Lam, Ph.D., all of MD Anderson's Department of Molecular and Cellular Oncology; Wei-Chao Chang, Ph.D., of China Medical University, Taichung, Taiwan, and Chung-Hsuan Chen, Ph.D., of Genomics Research Center of Academica Sinica, Taipei; Yun Wu, M.D., Ph.D., of MD Anderson's Department of Pathology; Brian James, Ph.D., Xiuping Liu, M.D., and Chang-Gong Liu, Ph.D., of MD Anderson's Department of Experimental Therapeutics; and Kotaro Nakanishi, Ph.D., and Dinshaw Patel, Ph.D., of Memorial Sloan-Kettering Cancer Center.
Shen is a graduate student at The University of Texas Graduate School of Biomedical Sciences at Houston, a joint program of MD Anderson and The University of Texas Health Science Center at Houston.
This research was funded by grants from the U.S. National Institutes of Health (CA109311 and CA099031), MD Anderson's Cancer Center Support Grant from the National Cancer Institute (CA16672), the U.S. National Breast Cancer Foundation, MD Anderson's Center for Biological Pathways, Susan G. Komen for the Cure, the Sister Institution Fund of China Medical University and Hospital and MD Anderson, the Taiwan Cancer Research Center of Excellence, a Private University grant from Taiwan and the Taiwan Program for Stem Cell and Regenerative Medicine Frontier Research.
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
When oxygen is short, EGFR prevents maturation of cancer-fighting miRNAsPublic release date: 23-May-2013 [ | E-mail | Share ]
Contact: Scott Merville smerville@mdanderson.org 713-792-0661 University of Texas M. D. Anderson Cancer Center
With tumor suppressors frozen in adolescence, resistant cancer cells cheat death
HOUSTON - Even while being dragged to its destruction inside a cell, a cancer-promoting growth factor receptor fires away, sending signals that thwart the development of tumor-suppressing microRNAs (miRNAs) before it's dissolved, researchers reported in an early online publication at Nature.
Under conditions of oxygen starvation often encountered by tumors, the epidermal growth factor receptor (EGFR) gums up the cell's miRNA-processing machinery, an international team led by scientists at The University of Texas MD Anderson Cancer Center discovered.
"So when hypoxia stresses a cell, signaling by EGFR prevents immature miRNAs from growing up to fight cancer," said senior author Mien-Chie Hung, Ph.D., professor and chair of MD Anderson's Department of Molecular and Cellular Oncology and holder of the Ruth Legett Jones Distinguished Chair.
The group's findings point to a potential new prognostic marker for breast cancer, Hung noted, but also provide the first evidence of a growth factor signaling pathway regulating miRNA maturation.
"Inside of a cell, you have signal induction, in this case through EGFR, and you also have a protein complex that processes precursors into mature miRNA to perform a function. They didn't appear to talk to each other, it's as if one speaks English and the other Chinese," Hung said. "This is the first paper to show how they communicate."
The scientists established the relationship in cell line experiments, confirmed it in a mouse model and human breast cancer samples, then found that it reduced breast cancer patient survival in a review of 125 cases.
A new cancer-promoting role identified for EGFR
EGFR penetrates the cell membrane to receive signals from growth factors outside of the cell. After a growth factor binds to it, EGFR conveys the signal into the cell by attaching phosphate groups to other proteins, often acting as a molecular "on switch."
In many cancers, EGFR is overexpressed or dysfunctional, constantly sending signals to cells to divide. Hung and colleagues found that EGFR also fuels cancer progression by stifling tumor-suppressing miRNAs.
As a tumor grows, large portions of its interior can become starved for oxygen (hypoxia) for lack of adequate blood vessels. This stress suffocates many tumor cells, but the few that endure become highly malignant, resist treatment and are most likely to spread, Hung said.
Anti-angiogenesis drugs designed to kill tumors by blocking their ability to spin webs of supportive blood vessels often succeed at first, Hung said, but then fail against the more malignant cells that survive hypoxia.
When hypoxia hits, EGFR gets active and gets eaten
Low-oxygen conditions cause EGFR overexpression. EGFR also is pulled into the cell interior, captured in cavities called vesicles and eventually fed into lysosomes, a membrane-enclosed organelle loaded with enzymes to dissolve proteins.
It was known that EGFR continues to signal even while caught in the vesicles, which actually prolongs its activation. Hung and colleagues found that EGFR signals to a key protein in miRNA processing called argonaute 2, or AGO2.
AGO2 connects with two other proteins called Dicer and TRBP to form a complex that processes microRNA precursors into mature miRNAs, which regulate gene expression after messenger RNA has been expressed but before it's translated into a protein.
Oncoprotein-regulating miRNAs don't grow up
The scientists found that EGFR attaches phosphate groups to AGO2, which in turn weakens AGO2's ability to connect with Dicer to produce mature microRNAs. EGFR's effect is stronger during oxygen starvation than under normal conditions.
The team identified a number of specific miRNAs affected by EGFR, most of which have been reported to have tumor suppressor characteristics. The miRNAs regulated by phosphorylated AGO2, including miR-31, miR-192 and miR-193a-5p, also shared a long-loop structure in their precursors that miRNAs unaffected by AGO2 phosphorylation lack.
Hypoxic environments around tumors promote metastasis by helping cells evade programmed cell death. Hung and colleagues showed that EGFR-mediated AGO2 phosphorylation blocks cell death and enhances invasiveness under hypoxia.
Experiments in a mouse model of breast cancer confirmed that expression of EGFR and the presence of phosphorylated AGO2 increase during tumor progression under oxygen-starved conditions.
EGFR-AGO2 connection found in human breast tumors; reduces survival
The hypoxia-EGFR-AGO2 connection was strong in tumor samples from 128 breast cancer patients, but it was low or absent in normal breast tissue. In 125 breast cancer cases analyzed by the team, half of 62 patients with high levels of phosphorylated AGO2 survived to 48 months and beyond. Median survival had not been reached for the 63 patients in the low-level group, but 78 percent had survived to 48 months.
"One can imagine other receptors for platelet-derived growth factor and insulin-like growth factor also regulating miRNAs, perhaps by regulating Dicer or TBRP," Hung said. "This is a turning-point paper; it will induce lots of new questions for scientists to pursue."
###
Co-authors with Hung are lead author Jia Shen, Weiya Xia, M.D., Yekaterina Khotskaya, Ph.D., Longfei Huo, Ph.D., Seung-Oe Lim, Ph.D., Yi Du, Ph.D., Yan Wang, Ph.D., Jennifer Hsu, Ph.D., and Yung Carmen Lam, Ph.D., all of MD Anderson's Department of Molecular and Cellular Oncology; Wei-Chao Chang, Ph.D., of China Medical University, Taichung, Taiwan, and Chung-Hsuan Chen, Ph.D., of Genomics Research Center of Academica Sinica, Taipei; Yun Wu, M.D., Ph.D., of MD Anderson's Department of Pathology; Brian James, Ph.D., Xiuping Liu, M.D., and Chang-Gong Liu, Ph.D., of MD Anderson's Department of Experimental Therapeutics; and Kotaro Nakanishi, Ph.D., and Dinshaw Patel, Ph.D., of Memorial Sloan-Kettering Cancer Center.
Shen is a graduate student at The University of Texas Graduate School of Biomedical Sciences at Houston, a joint program of MD Anderson and The University of Texas Health Science Center at Houston.
This research was funded by grants from the U.S. National Institutes of Health (CA109311 and CA099031), MD Anderson's Cancer Center Support Grant from the National Cancer Institute (CA16672), the U.S. National Breast Cancer Foundation, MD Anderson's Center for Biological Pathways, Susan G. Komen for the Cure, the Sister Institution Fund of China Medical University and Hospital and MD Anderson, the Taiwan Cancer Research Center of Excellence, a Private University grant from Taiwan and the Taiwan Program for Stem Cell and Regenerative Medicine Frontier Research.
[ | E-mail | Share ]
?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
NORTHAMPTON ? The annual Sojourner Truth Memorial Statue Celebration will be held May 26 at 2 p.m. in Florence.
A walking tour will precede the celebration at 12:30 p.m., starting at the Sojourner Truth statue on Pine Street. There will be music, dancing and a performance by the Enchanted Circle Theater.
Following the event there will be a reception at the David Ruggles Center.
Cancer clinic
NORTHAMPTON ? Cooley Dickinson Hospital is offering a free lecture on managing psychiatric disorders in patients with cancer on May 30 from 6 to 7 p.m. in the Dakin Conference Room.
Joseph A. Greer, a clinical psychologist from the Center for Psychiatric Oncology and Behavioral Sciences at the Massachusetts General Hospital Cancer Center, will discuss the presentation and treatment of the most common psychiatric disorders that patients with cancer experience, including adjustment, anxiety, and depressive disorders.
He will provide an overview of the Massachusetts General Cancer Center?s Center for Psychiatric Oncology and Behavioral Sciences and a review of current interventions that are designed to alleviate distress and enhance coping in patients living with a cancer diagnosis. Greer will be joined by Sean Mullally, MD, medical oncologist/hematologist, and medical director of the Cooley Dickinson Hospital Cancer Care Program.
The lecture is free and open to the public. Registration is required at www.cooley-dickinson.org/classes or (888) 554-4CDH (234).
Hilltown Idols
WILLIAMSBURG - The Williamsburg Grange will present Hilltown Idols! an adult and child Karaoke competition and fundraiser for the Williamsburg Elementary School.
Auditions are on June 8, the final performance on June 15 at 7 p.m. The competition is open to children and adults from near and far. There are four competition groups: Grades 3-5, 6-8, 9-12, & Adults. Prizes will be awarded to winners.
Entry fee for contestants in Grades 3-12 is $5. It?s $25 for adults. Register by June 1. Tickets for audience members on June 8 are $ for /individuals, $5 for families. Tickets for the final performance on June 15 are $5 for ages 3-18, $10 for adults, or $20 per family. See https://sites.google.com/site/hilltownidols for details.
Roast Beef Supper
NORTHAMPTON ? Florence Congregational Church will host a roast beef supper at 130 Pine St. on June 1 at 5:30 p.m.
Offerings are optional. For reservations, call (413) 584-1325.
![[ Back to EurekAlert! ]](https://lh3.googleusercontent.com/blogger_img_proxy/AEn0k_tDwB17OlpztRC1-YpSrDDhlO7tm7f3qyIkGSWGaDaest-TnQnduMLxfnECdUZQVjuED6dhCho3ZKaQOZvGLYfugJdy7REoA8C7tVhsiD0=s0-d){kind=small}
Public release date: 10-Jun-2013
Share ]