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Vasoactive intestinal peptide transactivates the androgen receptor through a PKA‐dependent extracellular signal‐regulated kinase pathway in prostate cancer cells
Author(s) -
Xie Yan,
Wolff Dennis W.,
Lin MingFong,
Tu Yaping
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a428-b
Subject(s) - lncap , androgen receptor , prostate cancer , transactivation , vasoactive intestinal peptide , endocrinology , medicine , androgen , cancer research , signal transduction , g protein coupled receptor , protein kinase a , receptor , biology , chemistry , microbiology and biotechnology , kinase , cancer , hormone , neuropeptide , biochemistry , transcription factor , gene
Transactivation of androgen receptor (AR) by growth factors acting through G‐protein coupled receptors (GPCRs) contributes to the development of androgen‐independent prostate cancer, the deadly form of this disease. Vasoactive intestinal peptide (VIP) is a survival factor for prostate cancer cells under androgen deprivation, but the molecular mechanisms underlying its facilitation of prostate cancer to an androgen‐independent state are unknown. We investigated the signaling pathway of VIP in LNCaP cells, a prostate cancer cell line that requires androgens for growth. Low nM concentrations of VIP, acting through G s ‐protein coupled VIP receptors, can induce LNCaP cell growth in the absence of androgen, a response that was nevertheless dependent on androgen‐independent activation of AR (EC 50 of 3.0 ± 0.8 nM). We then investigated signaling events downstream of VIP GPCRs that may interact with AR in LNCaP cells, finding that AR activation was PKA‐dependent and had contributions from ERK1/2. In addition, both ERK1 and ERK2 activation and androgen‐independent AR activation were dependent on PKA‐dependent Rap1 activation. Thus, VIP stimulation of G s ‐protein coupled VIP receptors linked to a PKA/Rap1/ERK1/2 pathway can cause androgen‐independent transactivation of AR, thereby promoting androgen‐independent proliferation of prostate cancer cells. NIH P20 RR018759 (Y.T., M.F.L.); NE State LB692 (Y.T.)