Receptor Role Revealed

Scientists Discover Key Event in Prostate Cancer Progression

A study led by researchers at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute (OSUCCC – James), and Dana-Farber Cancer Institute, reveals how malignant prostate tumors gain the ability to progress in the absence of androgen.

The onset of hormone-independent growth marks an advanced and currently incurable stage of prostate cancer.

In hormone-dependent disease, androgen receptors regulate an early phase of the cell cycle. In hormone-independent prostate cancer, the research shows, epigenetic changes reprogram the receptors to selectively regulate genes involved in mitosis.

One of those upregulated genes is UBE2C. This causes the cell to skip a mitotic check point, and it accelerates cell division.

“Some late-phase prostate cancers do not require androgen hormones for tumor growth, but they do require androgen receptors,” says first author and co-corresponding author Qianben Wang, PhD, assistant professor of Molecular and Cellular Biochemistry and a researcher with the OSUCCC – James. “Our study reveals that androgen-independent cancer cells aren’t directing androgen-dependent gene expression without androgen, but rather that they activate an entirely different pathway that results in androgen-independent growth.”

Wang, working with corresponding author Myles Brown, MD, professor of Medicine at Harvard Medical School and Dana-Farber Cancer Institute, and colleagues conducted the study using prostate cancer cell lines, gene expression data and human tumor tissue. Wang says the findings could identify new therapeutic targets and lead to new treatments for this lethal stage of the disease.

Published in the July 24, 2009, issue of the journal Cell.

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