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Could a tumor suppressor also fight obesity?
Date:8/25/2011

PHILADELPHIAThe hormone receptor guanylyl cyclase C (GCC) has been established as a suppressor of colorectal cancer tumors, but new evidence from Thomas Jefferson University suggests it may also help fight one of the country's biggest pandemics: obesity.

Reporting in the August 25 online issue of the Journal of Clinical Investigation, Scott Waldman, M.D., Ph.D., chairman of the Department of Pharmacology and Experimental Therapeutics at Jefferson, and colleagues found that silencing GCC affected appetite in mice, disrupting satiation and inducing obesity. Conversely, mice who expressed the hormone receptor knew when to call it quits at mealtime.

Revealing a never-before-shown endocrine axis between the intestine and hypothalamus, the research could provide novel therapeutic targets to control appetite, obesity and the metabolic syndrome, a promising notion, given that one-third of the U.S. population is considered obese.

Until now, the role of GCC outside the gut has remained elusive. Dr. Waldman and his team have previously shown its role as a tumor suppressor and biomarker that reveals occult metastases in lymph nodes. But its role in appetite is new and surprising territory.

"We were working with GCC-deficient mice to look at its role in tumorigenesis in the intestine," said Dr. Waldman. "Then the mice grew up, and we noticed something: They got fatter.

"We couldn't understand why it was happening, because GCC is expressed predominantly in intestine, and there was no indication that it regulated any function that had to do with metabolism and nutrient uptake."

To investigate this, Dr. Waldman, who also leads the Gastrointestinal Malignancies Program at the Kimmel Cancer Center at Jefferson, and his colleagues ra
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Contact: Steve Graff
stephen.graff@jefferson.edu
215-955-6300
Thomas Jefferson University
Source:Eurekalert

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