Androgen receptor activation by Gs signaling in prostate cancer cells

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 alpha subunit of heterotrimeric guanine nucleotide-binding G(S) protein activates the AR in prostate cancer cells and also synergizes with low concentration of androgen to more fully activate the AR. The G alpha(S) activates protein kinase A, which is required for the nuclear partition and activation of AR. These data suggest a role for G alpha(S) and PKA in the transactivation of AR in prostate cancer cells under the environment of reduced androgen levels.