Abstract
Obesity and prostate cancer exhibit a statistical link, which may be due to the paracrine/endocrine cell cycle effects of the adipocyte‐derived peptides leptin (LEP) and adiponectin (ADIPO). ADIPO induced AMPK–dependent phosphorylation of p27 on T198 (T198‐P) and increased total p27 protein and adiponectin receptor (ADIPOR1) protein levels in androgen‐receptor (AR) negative PC3 prostate cancer cells. Conversely, LEP induced the opposite effects on AMPK, T198‐P p27, total p27 and ADIPOR1 protein levels. LEP and ADIPO also had opposing effects in AR‐positive LNCaP cells. As observed in breast cancer cells, LEP treatment overcame the effects of ADIPO on all proteins examined in a concentration‐dependent manner. Furthermore, ADIPO administration was able to counteract the effects of LEP on all proteins measured. Our data suggest that ADIPO and LEP exert antagonistic effects on prostate epithelial cell cycle regulation, and modification of the ADIPO:LEP ratio may be one of the important factors that underlie the molecular link between obesity and prostate cancer progression.
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