Androgen receptor activation by G(s) signaling in prostate cancer cells |
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Authors: | Kasbohm Elizabeth A Guo Rishu Yowell Charles W Bagchi Gargi Kelly Patrick Arora Puneeta Casey Patrick J Daaka Yehia |
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Institution: | Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA. |
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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 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. |
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