The molecular contribution of TNF-α in the link between obesity and breast cancer.

Weichhaus, Michael; Broom, Iain; Bermano, Giovanna

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.

Citation

WEICHHAUS, M., BROOM, I. and BERMANO, G. 2011. The molecular contribution of TNF-α in the link between obesity and breast cancer. Oncology reports [online], 25(2), pages 477-483. Available from: https://doi.org/10.3892/or.2010.1099

• Journal Article Type: Article
• Acceptance Date: Oct 27, 2010
• Online Publication Date: Dec 10, 2010
• Publication Date: Feb 28, 2011
• Deposit Date: Feb 19, 2021
• Publicly Available Date: Jul 8, 2021
• Journal: Oncology Reports
• Print ISSN: 1021-335X
• Electronic ISSN: 1791-2431
• Publisher: Spandidos Publications
• Peer Reviewed: Peer Reviewed
• Volume: 25
• Issue: 2
• Pages: 477-483
• DOI: https://doi.org/10.3892/or.2010.1099
• Keywords: Obesity; Breast cancer; TNF-α
• Public URL: https://rgu-repository.worktribe.com/output/1148634
• Related Public URLs: http://hdl.handle.net/10059/591; https://rgu-repository.worktribe.com/output/1380292; https://rgu-repository.worktribe.com/output/1380312; https://rgu-repository.worktribe.com/output/1380321