Adiponectin has been shown to modulate angiogenesis and tumour cell behaviour. Breast and endometrial cancer patients have significantly decreased serum adiponectin levels, which may be important in such hormone-dependent cancers. Prostate cancer is another hormone-dependent cancer. Adiponectin orchestrates its actions by activating two seven-transmembrane receptors, adiponectin-R1 (adipo-R1) and adiponectin-R2 (adipo-R2). In this study we aim to determine adipo-R1/R2 expression in prostate cancer cell lines and the effect of various hormones/cytokines on their expression.
Using RT-PCR and Western blot we demonstrated for the first time the expression of adipo-R1 and adipo-R2 in the human prostate cancer cell lines PC-3 (androgen-independent) and LNCaP (androgen-dependent). Immunohistochemical analysis confirmed membrane localisation of both receptors in both cell lines. Cells were treated for 24 hours with dexamethasone, estradiol (E2), growth hormone, TNF-alpha and testosterone (100 nanomolar). Using real-time PCR we determined receptor expression at mRNA level in response to these treatments. Testosterone treatment resulted in increased mRNA levels of both receptors compared to basal in both cell lines. In PC-3 cells, E2 resulted in an increase in expression of both receptors, whereas TNF-alpha treatment resulted in a decrease of adipo-R2 expression alone. Growth hormone increased expression of both receptors in LNCaP. Interestingly, dexamethasone differentially modulated adiponectin receptor mRNA: expression of both receptors was increased in LNCaP, whereas adipo-R2 only was increased in PC-3.
In conclusion we demonstrate the presence of adiponectin receptors in prostate cancer cell lines, which suggests that adiponectin may exert its effects on the prostate gland, in an endocrine/paracrine manner. Furthermore, we provide novel evidence about the differential regulation of these receptors by hormones and cytokines. Further studies are required to investigate the potential role that adiponectin and its receptors may play in the aetiopathogenesis of prostate cancer.
04 - 06 Apr 2005
British Endocrine Societies