title: The molecular contribution of TNF-α in the link between obesity and breast cancer.
abstract: 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.
authors.affiliation: Centre for Obesity Research and Epidemiology (CORE), Faculty of Health and Social Care, Robert Gordon University, St. Andrew Street, Aberdeen, AB25 1HG, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Weichhaus
authors.forename: Iain
authors.initials: I
authors.lastname: Broom
authors.forename: Giovanna
authors.initials: G
authors.lastname: Bermano
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000097:blood / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018450:Disease Progression; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D009765:Obesity / Q000097:blood / Q000150:complications* / Q000378:metabolism; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000494:pharmacology / Q000502:physiology*
chemical_list: D014409:Tumor Necrosis Factor-alpha