Molecular links between obesity and breast cancer

For over 40 years there has been a statistical linkage between obesity and cancer, yet little is known about the molecular mechanisms underlying this long standing deleterious association. Recent work has shown that adipocyte‐derived peptides can affect cell cycle entry in mammary epithelial cells. Thus we examined the paracrine role of the adipokines leptin and adiponectin on mammary epithelial cell cycle regulation. G0 synchronized MCF7 cells were treated with leptin and adiponectin, separately and in concert, in time and dose dependent experiments. Immunoblotting demonstrated that p27 protein levels decreased with leptin treatment which suggested cell cycle entry. In contrast adiponectin increased p27 levels suggesting cell cycle arrest. To complement these experiments MCF7 cells were co‐cultured with subcutaneous adipocytes isolated from lean rats to mimic in vivo paracrine conditions. Moderate increases in adipocyte concentrations increased p27 levels up to a peak, mimicking the effects of adiponectin. At high adipocyte concentrations p27 levels decreased mirroring the effects of leptin. The relevance of these findings is that obese individuals exhibit high leptin levels and low adiponectin levels suggesting a stoichiometric imbalance may underlie cancer development and progression. This may also provide the basis for the development of novel cancer therapeutic and prevention strategies.