Premium
Effects of luteinizing hormone receptor signaling in prostate cancer cells
Author(s) -
Xiong Shigang,
Wang Qingcai,
Liu Stephen V.,
Montgomery Robert B.,
Stanczyk Frank Z.,
Vallone John G.,
Merin Noah M.,
Pinski Jacek
Publication year - 2015
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.22899
Subject(s) - lncap , androgen receptor , gene silencing , prostate cancer , androgen , endocrinology , cancer research , signal transduction , medicine , biology , chemistry , cancer , hormone , microbiology and biotechnology , biochemistry , gene
BACKGROUND The importance of androgen signaling in prostate cancer (PC) is well described and prostate cancer cells retain the ability to directly synthesize androgens. Luteinizing hormone (LH) can induce expression of steroidogenic enzymes and trigger androgen production, but the regulation of this process is not well‐described. Here, we explored the impact of silencing LH receptor (LHR) silencing on androgen synthesis and on several relevant signaling pathways in PC. METHODS LHR mRNA and protein expression was evaluated in LNCaP PC cells treated with LHR‐siRNA. MTS assay was used to measure the effect of LHR‐siRNA on proliferation in LNCaP and 22RV1 PC cells. Treated LNCaP and LAPC‐3 cells were also assayed for differences in androgen synthesis and expression of steroidogenic enzymes, PSA, AR, and critical signaling molecules including PKA, ERK1/2, PI3K, AKT2, and HER2. RESULTS We confirmed that functional LHR is expressed in both androgen‐sensitive and castrate‐resistant PC specimens. Treatment with LHR‐siRNA effectively silenced LHR gene and protein expression and prevented LH‐mediated proliferation and androgen synthesis in prostate cancer cells. LHR silencing also downregulated expression of AR, PSA, PKA, ERK1/2, PI3K, AKT2, and HER2. CONCLUSION Collectively, these data demonstrate that silencing LHR expression suppresses androgen synthesis and signaling and the LH‐LHR pathway may represent a viable therapeutic strategy in PC. Prostate 75:141–150, 2015 . © 2014 Wiley Periodicals, Inc.