Potential Prostate Cancer Blocker Identified

A protein that acts as a tumor suppressor when present in high concentration reduces the aggressiveness of prostate cancer and limits its tendency to metastasize.

Investigators at Kings College London (United Kingdom) have been studying the link between male hormones (androgens) and the growth and spread of prostate cancer. In a study published in the December 17, 2010, online edition of the journal Cancer Research they revealed results of experiments involving the RNA-binding protein FUS/TLS (Fused in Ewing's Sarcoma/Translocated in Liposarcoma). They had discovered that this protein was inhibited by androgens and wanted to learn whether it might be related to the effect of these hormones on prostate cancer cells.

Initial studies on cultures of prostate cancer cells showed that overexpression of FUS promoted growth inhibition and apoptosis. If FUS expression was blocked in prostate cancer cultures, its lack increased cell proliferation. This effect was reproduced in animal studies, which showed that increasing FUS levels in tumor xenografts led to dramatic tumor regression. Immunohistochemical analysis revealed that patients with high levels of FUS survived longer and were less likely to have bone metastases, suggesting that loss of FUS expression may contribute to cancer progression.

The investigators determined that at the molecular level FUS promoted conditions that favored cell-cycle arrest by reducing the levels of proliferative factors such as cyclin D1 and Cdk6 and by increasing levels of the antiproliferative Cdk inhibitor p27.

"These findings suggest that FUS might be able to suppress tumor growth and stop it from spreading to other parts of the body where it can be deadly. It is early stages yet but if further studies confirm these findings, then FUS might be a promising target for future therapies," said senior author Dr. Charlotte Bevan, reader in molecular oncology at Kings College London. "At the moment, there is no way to say whether a prostate tumor will kill you or be fairly harmless. Current hormonal therapies only work for a limited time, and chemotherapy is often ineffective against prostate cancer, so there is a real need for new treatments."

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