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A new route for tackling treatment-resistant prostate cancer
Date:7/24/2012

Professor in the Division of Endocrinology and Metabolism, knew from their previous research that paxillin is important in prostate cancer, but they didn't know why or how.

They found that under certain conditions the protein, which normally hangs out in the cytoplasm or gel-like substance that fills a cell, actually goes into the nucleus the cell's genetic powerhouse. There, it's an extremely commanding force, regulating signals that lead to the creation of cancer cells.

"This is the first time anyone's shown that paxillin goes into the nucleus and controls gene expression," said Sen. "When we eliminated this protein from prostate cancer cells their growth was significantly arrested, but what surprised us most was that this effect was identical in both hormone therapy-dependent as well as resistant prostate cancer cells."

In typical tumors stimulated by male hormones called androgens, paxillin partners with the hormones to turn on genes that lead to the creation of more cancer cells. Such tumors shrink, at least for a time, when subject to hormone therapy.

But for tumors that continue to grow despite hormone therapy called castration-resistant prostate cancer Hammes' team found that paxillin takes another route and connects with naturally occurring substances called growth factors to activate genes that produce more cancer cells.

Take paxillin out of the nucleus and growth comes to a halt: Without it, genes directed by androgens don't get turned on, nor do genes directed by growth factors.

"Lots of pathways are being examined as scientists look for what makes a prostate cancer cell become castration resistant, but ours is a completely novel approach," says Hammes of the paxillin-mediated pathway.

Sen adds, "We have now found a common factor that regulates both hormone-dependent and castration-resistant prostate cancer cells."

Edward M. Messing, M.D., chair of the Department of Urology
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Contact: Emily Boynton
emily_boynton@urmc.rochester.edu
585-273-1757
University of Rochester Medical Center
Source:Eurekalert

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