Androgen Receptor mRNA Causes Prostate Cancer Drug Resistance

A recent study describes the way that prostate cancer develops resistance to anti-androgen chemotherapy. This type of drug treatment prevents tumor growth by competing with testosterone, which promotes tumor growth, for binding to sites on the cancer cells.

Investigators at the University of California, Los Angeles (USA), transplanted human hormone-sensitive prostate cancers into mice using a technique known as xenografting. They then used DNA microarrays to monitor changes in gene activity as the tumors developed resistance to drug treatment.

They reported in the December 21, 2003, issue of Nature Medicine that a modest increase in androgen receptor mRNA was the only change consistently associated with the development of resistance to anti-androgen therapy. This increase in androgen receptor mRNA and protein was both necessary and sufficient to convert prostate cancer growth from a hormone-sensitive to a hormone-refractory stage, and was dependent on a functional ligand-binding domain.

"The microarray data pointed us to just one consistent change among all the xenografts,” said senior author Dr. Charles L. Sawyers, a professor at the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles. "And that was a change in the expression of the gene for the androgen receptor itself. We never really required that there even be one consistent change. We were fully prepared to find a signature of expression differences in some of the xenografts and another signature in others.”



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