Expression of resistin in the prostate and its stimulatory effect on prostate cancer cell proliferation.
OBJECTIVE
To determine whether resistin, a novel adipokine, induces prostate cancer cell proliferation. To identify the mechanisms underlying the activation of prostate cancer cells by resistin.


METHODS
Semi-quantitative reverse transcriptase-polymerase chain reaction and immunohistochemical staining were performed to investigate the intensity of prostate epithelial resistin expression. Human full-length resistin gene (RETN) was transfected into the PC-3 cells using the pEGFP-N1 vector to assess the effect of overexpression of resistin in prostate cancer cell line PC-3. Various concentrations of human recombinant protein resistin were added to the hormone-insensitive prostate cancer cell lines PC-3 and DU-145 for 48 h, and cell proliferation was assessed by a water-soluble tetrazolium salt assay.


RESULTS
Human prostate cancer cell lines PC-3 and DU-145 were found to express the human resistin mRNA. Resistin protein was strongly detected in high-grade prostate cancer tissue, whereas BPH or low-grade prostate cancer tissue revealed fainter expression of resistin. Cell proliferation was stimulated by both the full-length resistin gene overexpression and resistin treatment. Akt phosphorylation occurred after addition of resistin to PC-3 and DU-145 cells. LY294002, a pharmacological inhibitor of phosphatidylinositol 3-kinase (PI3K), significantly inhibited PC-3 and DU-145 cell proliferation after resistin treatment.


CONCLUSIONS
Resistin is expressed in human prostate cancers. Resistin induces prostate cancer cell proliferation through PI3K/Akt signalling pathways. The proliferative effect of resistin on prostate cancer cells may account in part for prostate cancer progression.
Advanced Urogenital Disease Research Center, Chung-Ang University College of Medicine, Seoul, Korea.
Hae Jong
HJ
Kim
Yong Seong
YS
Lee
Eun Ha
EH
Won
In Ho
IH
Chang
Tae Hyoung
TH
Kim
Eon Sub
ES
Park
Mi Kyung
MK
Kim
Wonyong
W
Kim
Soon Chul
SC
Myung
D049109:Cell Proliferation; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011467:Prostate / Q000473:pathology*; D011470:Prostatic Hyperplasia / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D052243:Resistin / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D052243:Resistin