Expression profiles and functional associations of endogenous androgen receptor and caveolin‐1 in prostate cancer cell lines. Issue 5 (24th December 2013)

• Record Type: Journal Article
• Authors: Bennett, Nigel C.; Hooper, John D.; Johnson, David W.; Gobe, Glenda C.
• Is Part Of: Prostate. Volume 74:Issue 5(2014)
• Page Start: 478
• Page End: 487
• Publication Date: 2013-12-24
• Subjects: Prostate -- Diseases -- Periodicals; 616
• DOI: 10.1002/pros.22767
• Languages: English
• ISSNs: 0270-4137

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="pros22767-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>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.</p> </sec> <sec id="pros22767-sec-0002" sec-type="section"> <title>METHODS</title> <p>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.</p> </sec> <sec id="pros22767-sec-0003" sec-type="section"> <title>RESULTS</title> <p>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.</p> </sec> <sec id="pros22767-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>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. <italic>Prostate 74:478–487, 2014</italic>. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>