BRCA1 Tumor Suppression Nullified By Cyclin D1 At The Estrogen Receptor

For about a decade, scientists have recognized that many cases of hereditary breast cancer result from a mutation of a specific gene called BRCA1, which, in its normal state, helps keep tumor formation in check. About five to 10 percent of breast cancer cases are linked to genetic miscues, about half of which are linked to BRCA1. But now scientists have discovered that a protein called cyclin D1, grossly overproduced in about half of all cases of breast cancer, can also disrupt BRCA1's normal role as a cancer inhibitor. The results reaffirm cyclin D1 as a candidate target for molecular therapeutic control of breast tumor development. "We've previously shown that if you have a gene therapy vector that blocks cyclin D1 in breast tumors induced by ErbB2 -- a common oncogene that many women have--you can block the growth of those tumors," said Richard Pestell, M.D., Ph.D., senior author of the paper published in the August 1 issue of Cancer Research and director of the Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, D.C. This paper, Pestell said, identifies the mechanism by which cyclin D1 nullifies the tumor suppressor activity of BRCA1. "Cyclin D1 is a collaborative oncogene and is sufficient for the induction of breast tumorogenesis in transgenic mice," he said. "This protein blocks the functional activity of the BRCA1 tumor suppressor. The science reported in this paper describes an important oncogene/tumor suppressor interaction."

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