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Dihydrotestosterone enhances castration‐resistant prostate cancer cell proliferation through STAT5 activation via glucocorticoid receptor pathway
Author(s) -
Song Cheryn,
Kim Yunlim,
Min Gyeong Eun,
Ahn Hanjong
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.22841
Subject(s) - du145 , lncap , dihydrotestosterone , androgen receptor , glucocorticoid receptor , cell growth , stat5 , chemistry , biology , cancer research , endocrinology , medicine , signal transduction , androgen , cancer cell , microbiology and biotechnology , prostate cancer , glucocorticoid , hormone , cancer , biochemistry
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. METHODS 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. RESULTS 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. CONCLUSION 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. Prostate 74:1240–1248, 2014 . © 2014 Wiley Periodicals, Inc.