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

Weichhaus, Michael; Broom, Iain; Bermano, Giovanna

Authors

Michael Weichhaus

Iain Broom



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 Mar 29, 2024
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

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