TY - JOUR AB - Obesity is a growing worldwide medical problem, as it pre-disposes the affected hosts to a number of severe diseases, including postmenopausal breast cancer. Obesity development is characterised, amongst others, by aberrant secretion of adipokines. White fat tissue infiltrating macrophages secrete tumour necrosis factor-α (TNF-α) so that its circulating levels correlate positively with body mass index (BMI). In the study presented here, the effect of TNF-α on cell proliferation, cell signalling pathway activation and cell cycle in two breast cancer cell lines and one breast epithelial cell lines was assessed to determine the contribution of TNF-α on breast cancer progression and aetiology, respectively. TNF-α acted differently on all three cell lines. In MDA-MB-231 breast cancer cells, cell proliferation and PI3-kinase activation were not affected, while MAP-kinase activation and cell cycle progression were decreased, with indications of increased apoptosis. This suggests a growth inhibitory function of TNF-α in these cells. In SK-BR-3 breast cancer cells, cell proliferation and cell signalling pathway activation increased, while cell cycle progression decreased, which contradictorily suggests both growth promoting and growth inhibiting properties of TNF-α on these cells. This makes TNF-α an unlikely candidate for a general contribution to the link between obesity and breast cancer progression, however, individual tumours may be responsive to a proliferative signal of TNF-α. In MCF-10A breast epithelial cells, cell proliferation and MAP-kinase activation increased, while cell cycle progression was unaffected. This suggests a strong proliferative response in these cells, suggesting the possibility that TNF-α may contribute to breast cancer aetiology as a novel link between obesity and increased risk of breast cancer development. AD - Centre for Obesity Research and Epidemiology (CORE), Faculty of Health and Social Care, Robert Gordon University, St. Andrew Street, Aberdeen, AB25 1HG, UK null AU - Weichhaus,Michael AU - Broom,Iain AU - Bermano,Giovanna DA - 2011/02/01 DO - 10.3892/or.2010.1099 EP - 483 IS - 2 JO - Oncol Rep KW - obesity breast cancer TNF-α PY - 2011 SN - 1021-335X 1791-2431 SP - 477 ST - The molecular contribution of TNF-α in the link between obesity and breast cancer T2 - Oncology Reports TI - The molecular contribution of TNF-α in the link between obesity and breast cancer UR - https://doi.org/10.3892/or.2010.1099 VL - 25 ER -