Dihydrotestosterone enhances castration‐resistant prostate cancer cell proliferation through STAT5 activation via glucocorticoid receptor pathway. Issue 12 (7th July 2014)

• Record Type: Journal Article
• Authors: Song, Cheryn; Kim, Yunlim; Min, Gyeong Eun; Ahn, Hanjong
• Is Part Of: Prostate. Volume 74:Issue 12(2014)
• Page Start: 1240
• Page End: 1248
• Publication Date: 2014-07-07
• Subjects: Prostate -- Diseases -- Periodicals; 616
• DOI: 10.1002/pros.22841
• Languages: English
• ISSNs: 0270-4137

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="pros22841-sec-0001" sec-type="section"> <title>INTRODUCTION</title> <p>We aimed to evaluate STAT5 expression and cell proliferation change after dihydrotestosterone (DHT) treatment in castration‐resistant prostate cancer (CRPC) cells to elucidate the mechanism in relation to different androgen receptor (AR) expression status.</p> </sec> <sec id="pros22841-sec-0002" sec-type="section"> <title>METHODS</title> <p>Using DU145, PC3, and LNCaP cells, cell viability assay and Western blot for phosphorylated STAT5 (p‐STAT5) were done after DHT treatment at various concentrations. Endogenous levels of nuclear hormone receptor mRNA and protein were identified using real‐time RT‐PCR and Western blot. We treated the cells with RU486 and then glucocorticoid receptor (GR)‐specific small interfering RNA (siRNA), to assess change in DHT‐induced STAT5 activation. Immunofluorescence staining of DU145 cells with anti‐GR and anti‐pSTAT5 Ab before and after DHT treatment was done and visualized.</p> </sec> <sec id="pros22841-sec-0003" sec-type="section"> <title>RESULTS</title> <p>DHT treatment enhanced STAT5 phosphorylation and promoted proliferation of all CRPC cells. Endogenous GR was identified strongly in DU145, weakly in PC3 but not in LNCaP cells. AR was identified strongly in LNCaP but not in DU145 cells. RU486 treatment abolished DHT‐induced cell proliferation and STAT5 activation in both DU145 and PC3 cells but not in LNCaP cells. Similarly, GR‐specific siRNA completely suppressed STAT5 activation. On immunofluorescence, activation of STAT5 and GR translocating into the nucleus after DHT treatment was confirmed. Immunoprecipitation confirmed direct complex formation between the GR and pSTAT5.</p> </sec> <sec id="pros22841-sec-0004" sec-type="section"> <title>CONCLUSION</title> <p>In CRPC cells, DHT activated STAT5 enhancing cell proliferation. Activation was induced regardless of presence of AR and in cells devoid of AR, DHT used GR which formed direct complex with p‐STAT5. <italic>Prostate 74:1240–1248, 2014</italic>. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>