A novel role for insulin resistance in the connection between obesity and postmenopausal breast cancer

Weichhaus,Michael; Broom,John; Wahle,Klaus; Bermano,Giovanna

doi:10.3892/ijo.2012.1480

A novel role for insulin resistance in the connection between obesity and postmenopausal breast cancer

Authors:
- Michael Weichhaus
- John Broom
- Klaus Wahle
- Giovanna Bermano
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Affiliations: Centre for Obesity Research and Epidemiology (CORE), Institute for Health and Welfare Research, Robert Gordon University, Aberdeen, UK, School of Medicine and Dentistry, College of Life Sciences and Medicine, Medical School, University of Aberdeen, Aberdeen, UK
Published online on: May 16, 2012 https://doi.org/10.3892/ijo.2012.1480
Pages: 745-752

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Abstract

The past two decades have seen a drastic increase in obesity rates in Western societies and emerging countries. As such, it has become increasingly important to understand the molecular mechanisms by which obesity affects the risk of developing associated co-morbidities. The present study aimed at identifying the effect of insulin on breast cancer and breast epithelial cells, reflective of obesity-associated hyperinsulinaemia, as a molecular explanation for the increased risk of oestrogen receptor-negative postmenopausal breast cancer in obese women. Both of the examined breast cancer cell lines (MDA‑MB-231 and SK-BR-3) showed intact insulin signalling (insulin receptor phosphorylation and activation of phosphoinositol-3 kinase and mitogen-activated protein kinase cell signalling pathways), with MDA-MB-231 cells showing aberrantly amplified insulin signalling. Insulin did not induce a physiologically significant change in proliferation or apoptosis in either cell line. MDA-MB-231 cells showed decreased cell proliferation and increased S-phase population, while SK-BR-3 cells showed increased cyclin D and cyclin E gene expression and increased necrosis after insulin treatment. Hyperinsulinaemia may not be a universal mechanism by which obesity affects breast cancer progression. Normal breast epithelial cells (MCF-10A) showed intact insulin signalling, increased cell proliferation and reduced apoptosis after insulin treatment, suggesting cell growth and survival-promoting effects of insulin on these cells. Thus, hyperinsulinaemia may affect breast cancer aetiology rather than progression and this finding may provide a novel molecular mechanism for the role of insulin in the promotion of increased postmenopausal breast cancer risk in obese women.

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