Leptin induces a proliferative response in breast cancer cells but not in normal breast cells

V. Dubois , T. Jarde , L. Delort , H. Billard , D. Bernard-Gallon , Emmanuelle Berger (1) , A. Geloen , M. P. Vasson , F. Caldefie-Chezet

1 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition

Obesity is a risk factor for breast cancer in postmenopausal women. Leptin, a hormone excessively produced during obesity, is suggested to be involved in breast cancer. The aim of the study was to investigate procarcinogenic potential of leptin by evaluating influence of leptin on cell proliferation, cell cycle, apoptosis, and signaling on numerous breast cells lines, including 184B5 normal cells, MCF10A fibrocystic cells and MCF-7, MDA-MB-231, and T47D cancer cells. Expressions of leptin and Ob-R were analyzed using qRT-PCR and immunohistochemistry, proliferation using fluorimetric resazurin reduction test and xCELLigence system, apoptosis and cell cycle by flow cytometry, and effect of leptin on different signalling pathways using qRT-PCR and Western blot. Cells were exposed to increasing concentrations of leptin. All cell lines expressed mRNA and protein of leptin and Ob-R. Leptin stimulated proliferation of all cell lines except for 184B5 and MDA-MB-231 cells. Leptin inhibited apoptosis but didn't alter proportion of cells within cell cycle in MCF7 cells. Leptin induced overexpression of leptin, Ob-R, estrogen receptor, and aromatase mRNA in MCF-7 and T47D cells. Autoregulation induced by leptin, relationship with estrogen pathway, and proliferative and antiapoptic activity in breast cancer cells may explain that obesity-associated hyperleptinemia may be a breast cancer risk factor.

Mots clés: Female; Humans; Cell Line; Tumor; Signal Transduction/drug effects; Apoptosis/drug effects; Immunohistochemistry; MCF-7 Cells; Breast Neoplasms/*blood/etiology; Cell Cycle/drug effects; Cell Proliferation/*drug effects; Fibrocystic Breast Disease/blood/etiology; Leptin/*blood/genetics; Obesity/*blood/complications; Receptors; Leptin/blood/genetics

Domaines: Sciences du Vivant [q-bio]

V. Dubois, T. Jarde, L. Delort, H. Billard, D. Bernard-Gallon, et al.. Leptin induces a proliferative response in breast cancer cells but not in normal breast cells. Nutrition and Cancer, 2014, 66 (4), pp.645-55. ⟨10.1080/01635581.2014.894104⟩. ⟨hal-01859390⟩