[PKD3 contributes to up-regulation of prostate-specific antigen in prostate cancer cells].
OBJECTIVE
To investigate the role of PKD3 in prostate-specific antigen (PSA) expression regulation in androgen-dependent prostate cancer cells and explore the mechanism.


METHODS
LNCaP cells containing low level of PKD3 were transfected with pEGFP-C2 or pEGFP-PKD3 plasmid followed by dihydrotestosterone (DHT) treatment, and PSA mRNA level was analyzed by RT-QPCR using 2(-delta delta Ct) method. Wild-type or kinase-dead PKD3 plasmids, human androgen receptor plasmid pSVAR0, pMMTV-luc of AR luciferase reporter and renilla luciferase reporter pRL-SV40 were cotransfected into HEK293 cells, and after treatment with DHT for 24 h, the cells were harvested and AR transcriptional activity were determined by dual-luciferase reporter assay. The subcellular localization of endogenous PKD3 and AR and their colocalization induced by DHT were observed by confocal microscopy.


RESULTS
PSA mRNA level triggered by DHT was significantly increased by overexpression of pEGFP-PKD3 in LNCaP cells compared with that in pEGFP-C2 control cells (P<0.001). AR transcription in response to DHT treatment was also significantly up-regulated by wild type PKD3 expression (P<0.001), but partially down-regulated by kinase-dead PKD3 mutant (P<0.01). Endogenous PKD3 and AR in LNCaP cells not only translocated from the cytoplasm to the nucleus, but also colocalized with each other after DHT stimulation.


CONCLUSIONS
Elevated AR transcriptional activity and enhanced expression of PSA induced by PKD3 in response to DHT treatment suggest that PKD3 contributes to the proliferation and malignant growth of androgen-dependent prostate cancer cells.
Deng
Fan
F
Department of Cell Biology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. fandeng@smu.edu.cn
Wang
Chun-xia
CX
Xu
Wan-fu
WF
Feng
Li
L
Ke
Zhi-yong
ZY
Wang
Q Jane
QJ
Zou
Zhi-peng
ZP
D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation
C119190:protein kinase C nu; D011493:Protein Kinase C; D017430:Prostate-Specific Antigen