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Amplification of a Stat5 gene produces excess oncogenic protein that drives prostate cancer spread
Date:5/7/2013

(PHILADELPHIA) An international group of investigators, led by researchers at Thomas Jefferson University's Kimmel Cancer Center, have solved the mystery of why a substantial percentage of castrate-resistant metastatic prostate cancer cells contain abnormally high levels of the pro-growth protein Stat5. They discovered that the gene that makes the protein is amplified duplicated many times over in these cancer cells, which allows them to produce excess amounts of the oncogenic protein.

The study, reported in the May 7 issue of the American Journal of Pathology, found a direct association between the number of Stat5 genes in human prostate cancer cells and Stat5 protein levels, and also revealed that gene amplification and protein levels increased as prostate cancer metastasized and became resistant to castration (anti-androgen) therapy.

The finding is important since agents that inhibit the Stat5 pathway are currently entering clinical trials, says the study's senior author, Marja Nevalainen, M.D., Ph.D., associate professor of Cancer Biology, Medical Oncology, and Urology at Jefferson.

"Our latest findings on Stat5 provide further support for the idea that targeting Stat5 protein pharmacologically might provide powerful therapy for advanced prostate cancer," she says. "Our hope is that a successful agent might prevent some prostate tumors from spreading and might be able to contain metastasis that has already occurred and become castrate-resistant."

The discovery also suggests that testing Stat5 gene amplification in patients could provide a biomarker that identifies those patients most likely to respond to Stat5 inhibition, Dr. Nevalainen says.

Not only is Dr. Nevalainen testing Stat5 inhibitors developed by Astra Zeneca and Novartis in preclinical studies, her lab has also developed its own inhibitor, which is also being tested.

Dr. Nevalainen has long studied Stat5 in prostate cancer, and with
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Contact: Jackie Kozloski
jackie.kozloski@jefferson.edu
215-955-5296
Thomas Jefferson University
Source:Eurekalert

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