From hormone-sensitive to hormone-refractory: how does it happen?

According to a press release from the Ohio State University Comprehensive Cancer Center, researchers at that center, in collaboration with  others at the Dana-Farber Cancer Institute in Boston, believe they have been able to reveal how late-stage, hormone-independent prostate tumors gain the ability to grow without need of hormones.

The study by Wang et al., to be published in the July 24, 2009, issue of the journal Cell, reports that androgen receptors are reprogrammed to regulate a group of genes involved in a different, later, phase of cell division, triggering rapid cell growth. “Some late-phase prostate cancer does not require androgen hormones for tumor growth, but it does require androgen receptors,” says Qianben Wang, assistant professor of molecular and cellular biochemistry and a researcher with the Ohio State University Comprehensive Cancer Center

Wang and his colleauges showed that, in hormone-dependent disease, androgen receptors regulate an early phase of the cell cycle. In hormone-independent prostate cancer, however, the receptors are reprogrammed to selectively regulate genes involved in actual cell division, that is, the mitotic phase of the cycle. A gene called UBE2C was a standout among these genes, and increased expression of that gene correlated with progression to the hormone-independent phase.

In addition, a chemical change – aso-called epigenetic change – in a particular histone protein associated with that gene enabled androgen receptors to bind with and activate the gene in hormone-independent prostate cancer. Over-expression of this gene is necessary for the growth of the hormone-independent prostate cancer cells.

“Interestingly,” Wang says, “the UBE2C gene is also over-expressed in breast, lung, ovary, bladder, thyroid and esophageal cancers, suggesting that our findings could have wide application.”

The “New” Prostate Cancer InfoLink would point out that we are gradually expanding our detailed knowledge of a variety of things that occur at the cellular level as patients progress from hormone-sensitive to hormone-refractory prostate cancer, but we have a  ways to go before we can tell exactly how to use this knowledge effectively to develop drugs or biologic agents that can accurately stop or reverse the biologic processes that lead to hormone-refractory disease.

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