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

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 ng{combining long solidus overlay}ml) 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 ng{combining long solidus overlay}ml) was observed. Cell proliferation was not affected at supraphysiological leptin concentrations (>800 ng{combining long solidus overlay}ml) 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 ng{combining long solidus overlay}ml). 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.

Citation

WEICHHAUS, M., BROOM, J., WAHLE, K. and BERMANO, G. 2014. Leptin inhibits proliferation of breast cancer cells at supraphysiological concentrations by inhibiting mitogen-activated protein kinase signaling. Oncology letters [online], 8(1), pages 374-378. Available from: https://doi.org/10.3892/ol.2014.2085

• Journal Article Type: Article
• Acceptance Date: Feb 18, 2014
• Online Publication Date: Apr 25, 2014
• Publication Date: Jul 31, 2014
• Deposit Date: Mar 11, 2015
• Publicly Available Date: Mar 11, 2015
• Journal: Oncology letters
• Print ISSN: 1792-1074
• Electronic ISSN: 1792-1082
• Publisher: Spandidos Publications
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Issue: 1
• Pages: 374-378
• DOI: https://doi.org/10.3892/ol.2014.2085
• Keywords: Leptin; Breast cancer; Obesity; Cell proliferation; Mitogen-activated protein kinase cell signaling pathway
• Public URL: http://hdl.handle.net/10059/1160