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BRCA1 gene found to inhibit two sex hormones, not just one

It's been known that the breast cancer susceptibility gene BRCA1 regulates use of estrogen in breast and other cells, but now researchers at Georgetown University Medical Center have discovered that it also controls activity of a second sex steroid hormone, progesterone.

The findings, conducted in cell culture and in mice and reported by the researchers in the January issue of Molecular Endocrinology, could help explain why women who have mutations in their BRCA1 gene are susceptible to a number of different "hormone-dependent" cancers, including those of the breast, endometriun and cervix.

It also has implications for ordinary cancers that arise because a normal BRCA1 gene is under-expressed, said the study's principal investigator, Eliot Rosen, MD, PhD, professor of oncology, cell biology, and radiation medicine at the Lombardi Comprehensive Cancer Center.

For example, he says that up to 40 percent of breast tumors are deficient in BRCA1, "and it may be that some patients could benefit not only from an anti-estrogen therapy, like tamoxifen, but also from an anti-progesterone agent.

"We don't know if that is true yet, of course, but it is certainly worth investigating, given our findings," Rosen said.

The BRCA1 gene and a second gene, BRCA2, were discovered to be breast cancer susceptibility genes in 1994 and 1995, respectively. Women who inherit faulty copies of one of these genes have up to an 80 percent increased risk of developing breast cancer by age 70, and are also more likely to be diagnosed with ovarian cancer.

Rosen and his research team undertook the study to understand why loss of the BRCA1 gene results in cancers in tissues that are dependent on hormones. They focused on the progesterone hormone, in part, because of the observation that women who use hormone replacement therapy that includes both estrogen and progestin (a synthetic form of progesterone) are at greater risk of developing breast cancer tha
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Contact: Liz McDonald
eem6@georgetown.edu
202-687-5100
Georgetown University Medical Center
26-Jan-2006


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