Effects of luteinizing hormone receptor signaling in prostate cancer cells.
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.


CONCLUSIONS
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.
Norris Comprehensive Cancer Center and Keck School of Medicine, Division of Medical Oncology, University of Southern California, Los Angeles, California.
Shigang
S
Xiong
Qingcai
Q
Wang
Stephen V
SV
Liu
Robert B
RB
Montgomery
Frank Z
FZ
Stanczyk
John G
JG
Vallone
Noah M
NM
Merin
Jacek
J
Pinski
D000728:Androgens / Q000096:biosynthesis; D000818:Animals; D020868:Gene Silencing / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D011974:Receptors, LH / Q000096:biosynthesis* / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000728:Androgens; D034741:RNA, Small Interfering; D011974:Receptors, LH
HER2; androgen receptor; androgen synthesis; luteinizing hormone; prostate cancer