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Loss of cell adhesion protein drives esophageal and oral cancers in mice
Date:4/12/2011

PHILADELPHIA - Squamous cell cancers of the oral cavity and esophagus are common throughout the world, with over 650,000 cases of oral cancer each year and esophageal cancer representing the sixth most common cause of cancer death in men. Research by University of Pennsylvania School of Medicine investigators has shown that a protein that helps cells stick together is frequently absent or out of place in these cancers, but it's unclear if its loss causes the tumors.

The investigators report that mice engineered to lack this protein, called p120-catenin (p120ctn), in the oral-upper digestive tract develop squamous cell cancers. The data, reported Cancer Cell, settle a 20-year debate and prove that p120ctn is a tumor-suppressor protein. What's more, the tumors that form in this mouse model closely resemble human disease and may point the way to novel therapies and early detection strategies.

"As the mice aged, what we saw was a dramatic evolution of precancer to cancer," says senior author Anil K. Rustgi, MD, the T. Grier Miller Professor of Medicine and Genetics and chief of Gastroenterology. "Both the precancerous growth, called dysplasia, and the cancer look exactly like what we see in humans. This is really exciting because it supports efforts for prevention and early detection, especially in people who drink alcohol and smoke cigarettes excessively and are at high risk for the disease in many regions of the world."

In healthy tissues, p120ctn is part of a protein complex that holds epithelial cells in tightly packed sheets. When p120ctn (or another of these cell adhesion proteins) is lost, a wide variety of cancers including those in prostate, breast, pancreas, colon, skin, bladder, and the endometrium, can result.

The cells lose their tight cell-cell contacts and can migrate more easily, which likely favors cancer spread and invasion of new cells. However, earlier attempts to test the effects of p120ctn loss on cancer f
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert

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