New Way to Treat Hormone Refractory Prostate Cancer
Reported April 13, 2009
(Ivanhoe Newswire) — There may be a new way to treat advanced forms of prostate cancer.
Scientists from the University of Maryland School of Medicine have found a protein that modifies the androgen receptor (AR) and influences how it regulates target genes linked with the progression of prostate cancer. The research may also help create new ways to treat advanced prostate cancer that no longer responds to traditional anti-hormone therapies.
The AR is an important link in the development and progression of prostate cancer, including when the disease turns into the aggressive and often deadly androgen-independent form.
Androgen ablation therapy is the most common treatment for advanced prostate cancer, senior study author, Dr. Yun Qiu, the University of Maryland School of Medicine, was quoted as saying. However, many patients inevitably develop deadly recurrent cancers, which no longer respond to androgen blockade and are resistant to current therapy.
When researchers looked for proteins that interact with the AR in hormone-refractory prostate cancer cells, they found RNF6 as an AR associated protein and showed that it induced ubiquitination of the AR and promoted AR transcriptional activity. Ubiquitination is a common protein modification that mediates a wide range of cellular activities. It is known to promote protein degradation, but the study found ubiquitination of AR by RNF6 seemed to have a stabilizing effect on AR protein.
Results also show the expression of RNF6 was higher in human prostate cancer tissues that do not respond to androgen ablation and is required for prostate tumor growth under androgen depleted conditions.
The authors conclude the findings implicate RNF6 as an important regulator of AR transcriptional activity, and that targeting parts of the ubiquitination machinery, such as RNF6, may be effective in treating advanced prostate cancer.
SOURCE: Cancer Cell, 2009;15:270-282