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Why a common treatment for prostate cancer ultimately fails
Date:8/21/2008

port cells known as stromal cells stimulates growth of cells, including cancer cells, in the prostate. He also found, surprisingly, that the receptor actually acts as a tumor suppressor in epithelial cells known as basal cells in the prostate.

Then Chang's team knocked out the androgen receptor in specific sets of prostate cells and studied the results. As expected, when the molecule is turned off in stromal cells, growth of cancer cells in the prostate slows. But when the molecule is turned off in the epithelial cells, it removes one of the body's natural inhibitors that prevents prostate cancer cells from spreading, making cells more likely to invade other tissues.

"While the androgen receptor is really driving prostate cancer, in another sense it appears that the receptor also normally inhibits the spread of cancer cells. It seems to have a dual role. Manipulating the androgen receptor can increase or decrease either of these actions depending on precisely how it's done," said Messing.

Chang says the molecule's versatility in the prostate should not come as a surprise, since the molecule's function elsewhere depends on its location.

"The effects of the androgen receptor on hair growth in men vary dramatically depending on where in the body the receptor is working," said Chang. "When the receptor is very active in the mustache area, more hair grows. When it's very active on the top of the skull, toward the front, hair falls out and men become bald. And the hair on the back of the head is insensitive to the receptor. The effects of hormones depend on the location.

"We found that the same is true within the cells of the prostate itself," said Chang, who is a faculty member in the departments of Urology and Pathology and the James P. Wilmot Cancer Center.

Chang says it's likely that the androgen receptor works differently in different cells partly because the assortment of molecular colleagues it works with within
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Contact: Leslie White
Leslie_White@urmc.rochester.edu
585-273-1119
University of Rochester Medical Center
Source:Eurekalert

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