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Expression profiles and functional associations of endogenous androgen receptor and caveolin‐1 in prostate cancer cell lines
Author(s) -
Bennett Nigel C.,
Hooper John D.,
Johnson David W.,
Gobe Glenda C.
Publication year - 2014
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.22767
Subject(s) - du145 , lncap , gene knockdown , androgen receptor , prostate cancer , androgen , biology , endogeny , cancer research , endocrinology , cell culture , medicine , chemistry , cancer , hormone , genetics
BACKGROUND In prostate cancer (PCa) patients, the protein target for androgen deprivation and blockade therapies is androgen receptor (AR). AR interacts with many proteins that function to either co‐activate or co‐repress its activity. Caveolin‐1 (Cav‐1) is not found in normal prostatic epithelium, but is found in PCa, and may be an AR co‐regulator protein. METHODS We investigated cell line‐specific signatures and associations of endogenous AR and Cav‐1 in six PCa cell lines of known androgen sensitivity: LNCaP (androgen sensitive); 22Rv1 (androgen responsive); PC3, DU145, and ALVA41 (androgen non‐reliant); and RWPE1 (non‐malignant). Protein and mRNA expression profiles were compared and electron microscopy used to identify cells with caveolar structures. For cell lines expressing both AR and Cav‐1, knockdown techniques using small interfering RNA against AR or Cav‐1 were used to test whether diminished expression of one affected the other. Co‐sedimentation of AR and Cav‐1 was used to test their association. A reporter assay for AR genomic activity was utilized following Cav‐1 knockdown. RESULTS AR‐expressing LNCaP and 22Rv1 cells had low endogenous Cav‐1 mRNA and protein. Cell lines that expressed little or no AR (DU145, PC3, ALVA41, and RWPE1) expressed high endogenous levels of Cav‐1. AR knockdown in LNCaP cells had little effect on Cav‐1, but Cav‐1 knockdown inhibited AR expression and genomic activity. CONCLUSIONS These data show endogenous AR and Cav‐1 mRNA and protein expression is inversely related in PCa cells, with Cav‐1 acting on the androgen/AR signaling axis possibly as an AR co‐activator, demonstrated by diminished AR genomic activity following Cav‐1 knockdown. Prostate 74:478–487, 2014 . © 2013 Wiley Periodicals, Inc.