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Cancer gene MYC emerging as key research target

PHILADELPHIA--First discovered twenty years ago, the cancer gene MYC is the most overexpressed oncogene in human cancers. But only in recent years have scientists begun to unravel MYC's complex workings in an effort to develop therapies that would block MYC's function in cancer. The promise of therapies targeting MYC appears especially great; MYC mutations are associated with a wide range of common cancer types, including breast, colon, ovarian and prostate cancers, and melanoma.

Recent studies have determined that the MYC protein, known as a transcription factor, binds to about 15 percent of all genes. Scientists had long believed that when MYC binds to a target gene, it turns that gene on, or activates it. Surprisingly, new work by Steven B. McMahon, Ph.D., assistant professor at The Wistar Institute, and others demonstrates that MYC frequently binds to genes without activating them. In an article for Nature Reviews Cancer published online today and in the July print issue, McMahon's research team offers a reanalysis of several previous studies of MYC's binding to target genes. The unexpected discovery that MYC binds to a large percentage of genes without activating them calls into question long-held assumptions about MYC's functioning and opens new directions for MYC research, McMahon says.

"These previous studies looked at which genes are bound by MYC, and it turns out to be a great percentage of genes--one out of every six," McMahon says. "Our work has extended what these studies hinted at: contrary to what was believed, MYC doesn't always turn on the genes to which it binds. The implication is that just figuring out which genes bind to MYC will not be enough to tell us what pathways are being activated in cancer. There must be other factors that play a role in whether MYC activates a gene."

McMahon worked with colleague Louise C. Showe, Ph.D., associate professor at The Wistar Institute and scientific director of Wistar's genomics and m
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Contact: Marion Wyce
wyce@wistar.upenn.edu
215-898-3943
The Wistar Institute
1-Jul-2004


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