Leptin inhibits proliferation of breast cancer cells at supraphysiological concentrations by inhibiting mitogen‑activated protein kinase signaling

Weichhaus,Michael; Broom,John; Wahle,Klaus; Bermano,Giovanna

doi:10.3892/ol.2014.2085

Leptin inhibits proliferation of breast cancer cells at supraphysiological concentrations by inhibiting mitogen‑activated protein kinase signaling

Authors:
- Michael Weichhaus
- John Broom
- Klaus Wahle
- Giovanna Bermano
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Affiliations: Centre for Obesity Research and Epidemiology (CORE), Institute for Health and Welfare Research, Robert Gordon University, Aberdeen AB10 7GJ, UK , Cancer Medicine Research Group, School of Medicine and Dentistry, University of Aberdeen, Medical School, Aberdeen AB25 2ZD, UK
Published online on: April 25, 2014 https://doi.org/10.3892/ol.2014.2085
Pages: 374-378

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Abstract

Leptin is a hormone secreted by white fat tissue and signals the amount of overall body fat to the hypothalamus. The circulating concentration of leptin correlates with the level of obesity. Breast cancer risk is higher in obese postmenopausal women compared with postmenopausal women of a normal weight, and high leptin concentrations may contribute to this risk. In the present study, SK‑BR‑3 and MDA‑MB‑231 breast cancer cell lines were treated with various concentrations (6.25‑1,600 ng̸ml) of recombinant leptin and changes in cell proliferation were assessed. The SK‑BR‑3 breast cancer cells exhibited a concentration‑dependent increase in proliferation with physiological leptin concentrations (<100 ng̸ml), but no further increase in proliferation at high leptin concentrations (>100 ng̸ml) was observed. Cell proliferation was not affected at supraphysiological leptin concentrations (>800 ng̸ml) in SK‑BR‑3 cells, whereas it decreased in MDA‑MB‑231 cells. Therefore, cell signaling and cell cycle changes were assessed at supraphysiological concentrations (1,600 ng̸ml). In the two cell lines, leptin treatment decreased the mitogen‑activated protein kinase (MAPK) cell signaling pathway activation. Leptin treatment did not increase Akt phosphorylation or significantly alter the cell population distribution across cell cycle stages. To the best of our knowledge, leptin‑induced growth inhibition of breast cancer cells at supraphysiological concentrations has not been reported in the literature to date, and the findings of this study suggest that reduced MAPK activity may be the underlying cause. Thus, the effect of leptin on breast cancer growth warrants further investigation since leptin is considered to be one of the main mediators in the obesity‑breast cancer connection.

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