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Study proposes new ovarian cancer targets
Date:3/13/2014

n ovarian cancer. TAF2 amplifications, copy number gains, and expression increases are present in 73 percent of tumors. TAF4 is amplified or upregulated in 66 percent of tumors, and TAF4B is amplified or upregulated in 26 percent. TAF9, meanwhile, is rendered significantly less expressed in 98 percent of ovarian tumors.

The ups and downs of TAF expression alone might not be that interesting if TAF activity didn't have any mechanistic influence in cancer cell biology. But in her review of scores of studies and further original research, Ribeiro presents reasons to believe that in specific tissues and contexts around the body, these TAFs take on roles that are relevant.

"They are not just general transcription factors," Freiman said. "They do much more specific things."

The worst tumors are ones in which cells have "dedifferentiated," which means they've lost their specific identities and reverted to a more generic, stem cell-like form. Sure enough, Ribeiro and Freiman have found that TAFs such as TAF4 and TAF4B are downregulated when stem cells differentiate. That makes their upregulation in ovarian tumors suspicious.

TAF4B also emerges as a cancer suspect in the study because of its apparent role in promoting cell proliferation, a major problem in the runaway cell multiplication in tumors. Lindsay Lovasco, a postdoctoral fellow at Brown and second author of the study, ran an experiment in mouse models where she removed some of the liver and measured whether TAFs expression changed while the tissue regenerated. Expression of Taf4b (the gene in mice) did increase significantly. Also, in human ovarian granulosa cell-derived tumors, in collaboration with Dr. Barbara Vanderhyden at the University of Ottawa, Ribeiro found that TAF4B expression correlates strongly with Cyclin D2 expression, a protein that specifically promotes granulosa cell proliferation.

Even more suspicion falls on TAF4B based on Ribeiro's finding published l
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Contact: David Orenstein
david_orenstein@brown.edu
401-863-1862
Brown University
Source:Eurekalert  

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