Leptin and adiponectin interact in regulating prostate cancer cell growth
Tina Mistry1, Janet Digby1, Ken Desai2 & Harpal Randeva1
Introduction: Leptin and adiponectin have opposing properties and are implicated as molecular mediators between obesity and (aggressive) prostate cancer. Adiponectin, circulates inversely proportional to visceral fat accumulation, and has demonstrated anti-proliferative effects in prostate cancer cells; circulating leptin levels increase with visceral fat accumulation and has shown mitogenic effects. We propose that adiponectin and leptin interact in prostate cancer cell growth regulation.
Materials and Methods: We studied the effect of full-length (fAd) and globular (gAd) adiponectin (0.01 nM100 nM) ± 100 nM leptin on LNCaP and PC3 prostate cancer cell proliferation. p53 tumour suppressor and bcl-2 oncogene expression was measured using quantitative RT-PCR.
Results: LNCaP: co-incubation of fAd with leptin resulted in decreased cell proliferation; fAd alone had little effect. gAd alone slightly increased proliferation and had little effect when co-incubated with leptin. fAd alone increased p53 mRNA expression and rescued leptin-induced inhibition of p53 expression; both fAd and gAd alone increased bcl-2 expression, but reduced expression to below basal when co-incubated with leptin. PC3: fAd decreased proliferation at 100nM, but reduced proliferation to half of basal when co-incubated with leptin; gAd alone increased proliferation but reduced proliferation to basal when co-incubated with leptin. Both fAd and gAd demonstrated significant dose-dependent increases in p53 mRNA expression when co-incubated with leptin; both fAd and gAd reduced bcl-2 expression to negligible levels despite the addition of leptin.
Conclusion: We show an interaction between adiponectin and leptin in the regulation of prostate cancer cell proliferation through modulation of p53 and bcl-2 expression; this is most marked in the advanced PC3 cell line. Concurrent hyperleptinaemia and hypoadiponectinaemia in obese patients may modulate prostate cancer progression, and serum leptin:adiponectin ratio could represent a new prognostic marker; increasing circulating fAd in these patients may be a novel treatment for this disease.