Leptin and adiponectin interact in the regulation of prostate cancer cell growth via modulation of p53 and bcl-2 expression.
OBJECTIVE
To investigate the effects of leptin, full-length adiponectin (fAd) and globular adiponectin (gAd), alone and in combination, on LNCaP and PC3 prostate cancer cell proliferation, and on the expression of p53 and bcl-2 gene expression.


METHODS
LNCaP and PC3 prostate cancer cells were cultured and treated with the following: 0-100 nM leptin; 0-100 nM fAd +/- 100 nM leptin; 0-100 nM gAd +/- 100 nM leptin. Proliferation assays and quantitative reverse transcriptase-polymerase chain reaction for p53 tumour-suppressor gene and bcl-2 oncogene expression were performed on treated samples.


RESULTS
Co-incubation of PC3 cells with 100 nM leptin and 1 or 100 nM fAd significantly decreased cell proliferation to approximately half of basal (P < 0.001); there was no significant effect in LNCaP cells. Leptin-induced inhibition of p53 expression in LNCaP cells was rescued by fAd. Leptin and fAd dose-dependently potentiated p53 expression in PC3 cells (P < 0.001); leptin and gAd also increased p53 expression (P < 0.05 and P < 0.001). fAd and gAd had no effect on bcl-2 expression in the presence of leptin in LNCaP cells. In PC3 cells, bcl-2 expression was inhibited to negligible levels in the presence of leptin.


CONCLUSIONS
Leptin and adiponectin interact, resulting in the inhibition of prostate cancer cell proliferation, particularly in PC3 cells, via modulation of p53 and bcl-2 expression. Our findings support the notion that high leptin and low adiponectin levels may be important in driving obesity-related prostate cancer progression.
Mistry
Tina
T
Department of Urology, University Hospital Coventry and Warwickshire, Coventry, UK. mistrytina@hotmail.com
Digby
Janet E
JE
Desai
Ken M
KM
Randeva
Harpal S
HS
D052242:Adiponectin / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000150:complications* / Q000378:metabolism; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000150:complications / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D052242:Adiponectin; D020738:Leptin; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53