Androgen receptor activation by Gs signaling in prostate cancer cells

Abstract

The androgen receptor (AR) is activated in prostate cancer patients undergoing androgen ablative therapy and mediates growth of androgen-insensitive prostate cancer cells, suggesting it is activated by nonandrogenic factors. We demonstrate that activated α subunit of heterotrimeric guanine nucleotide-binding Gs protein activates the AR in prostate cancer cells and also synergizes with low concentration of androgen to more fully activate the AR. The Gαs activates protein kinase A, which is required for the nuclear partition and activation of AR. These data suggest a role for Gαs and PKA in the transactivation of AR in prostate cancer cells under the environment of reduced androgen levels. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.