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SFVAMC study explains prostate cancer resistance to hormone therapy

Hormone therapy is often used to treat prostate cancer, but these drugs that mimic the effects of estrogen do not work on many late-stage cancers. Now San Francisco Veterans Affairs Medical Center researchers say they can explain the failure of these drugs, and suggest a way to restore their potency.

The study, published in the latest issue of Journal of the National Cancer Institute, reveals that late-stage prostate cancer is unresponsive to hormone therapy because the cells have shut down genes for the estrogen receptors where the drugs act.

The genes are switched off by a process called hypermethylation, a well-known process in which numerous methyl groups are attached to the regulatory stretches of DNA near the beginning of the gene, said the studys lead author Raj Dahiya, PhD, director of the urology research center at SFVAMC, and UCSF professor of urology.

This hypermethylation explains why we see inactivation of estrogen receptors in prostate cancer, and why hormone therapy no longer works in many cases, said Dahiya, whose research was supported by funding from the Department of Veterans Affairs, and by grants from the National Institutes of Health, which were managed by Northern California Institute for Research and Education (NCIRE).

In their study, Dahiyas group first showed that normal prostate cells were free of methylation at estrogen receptor genes and the cells displayed plenty of estrogen receptors. However, cells from late-stage prostate cancers had hypermethylation on their estrogen receptor genes and the cells displayed no estrogen receptors. Cells from an early stage prostate cancer have some methylation, which leads to intermediate activity, and the generation of relatively few estrogen receptors, Dahiya said.

Studies of prostate tissue taken from 38 prostate cancer patients further strengthened the link between hypermethylation and prostate cancer. The researchers found that nearly all tissue samp
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Contact: Kevin Boyd
kboyd@pubaff.ucsf.edu
415-476-8429
University of California - San Francisco
6-Mar-2002


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