A study at The Cleveland Clinic has discovered that a gene – known as an androgen receptor (AR) is present in both breast and prostate cancers, but the gene has opposite effects on these diseases.
The AR gene promotes prostate cancer when the gene is “turned on,” but in breast cancer the AR gene promotes cancer growth when the gene is “turned off.”
Prostate cancer often borrows treatments from breast cancer. However, in treating AR in prostate and breast cancers the treatments need to be completely opposite. In treating prostate cancer, the strategy should be to block AR; in breast cancer, the strategy should be to support AR production.
The researchers from Cleveland Clinic’s Lerner Research Institute, including Charis Eng, M.D., Ph.D., Chair, Genomic Medicine Institute; Robert Silverman, Ph.D., and Warren Heston, Ph.D., both of the Department of Cancer Biology; focused their study on whether the androgen receptor (AR) molecule offers evidence of the tumor suppressor protein PTEN. The research discovered that AR inhibits PTEN expression in prostate cancer cells, but stimulates it in breast cancer cells.
Their conclusions, published in the Oct. 21, 2011 issue of Oncogene, explain why prostate cancer progression is associated with increased AR expression (and a common prostate cancer treatment strategy involves blocking AR), while most breast cancers occur post-menopause, after AR production has ceased (making AR supplementation a strategy for treating breast cancer).
The researchers mapped the interaction between AR and PTEN in both prostate and breast cancer cells, which suggests that this interaction activates or represses subsequent gene expression depending on organ-specific cofactors. Although PTEN is a known tumor suppressor, and loss of PTEN expression has been associated with numerous cancers (including breast and prostate cancers), its regulation has not been well understood. The current data provide new information regarding PTEN regulation, and suggest that identifying regulatory cofactors will be a valuable next step in determining cancer risk, as well as potential new therapies.
“We now see how androgen affects PTEN expression – and ultimately cancer,” said Dr. Eng. “Our observations help explain why this prostate cancer risk can be halved by drinking red wine, which increases PTEN expression. Our data also suggest that treatment of the exact same cancer must be personalized for males and for females.”
Joel T. Nowak, M.A., M.S.W.