Westerhoff, S. (Susanne) (2014) IGFBP-2 regulation by glucose and leptin in breast cancer cells and its potential role in the obesity-cancer link. thesis, Medicine.
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Abstract
Introduction: Obesity is associated with an increased risk of cancer. Leptin levels are increased in obese subjects and chronically elevated leptin has been shown to promote cancer progression. IGFBP-2 has been shown to be regulated by leptin and is highly expressed in several forms of cancer. Recent studies in prostate cancer cells, have demonstrated that hyperglycaemia, common in obesity, can cause chemo-resistance, an event mediated via up regulation of IGFBP-2. Other studies have shown that hyperglycaemia can enhance leptin signalling in cancer cells. The aim of this study is to investigate the interactions between glucose and leptin in modulation of IGFBP-2 expression in breast cancer cells. Methods: MCF-7 breast cancers cells were treated with three different glucose levels (5 mM, 15 mM or 25 mM) with our without three different doses of leptin (5 nM, 12.5 nM or 25 nM). IGFBP-2 mRNA expression was assessed by RT-qPCR and IGFBP-2 protein levels by Western immunoblotting. MTT proliferation assay was used to assess cell proliferation. Results: The data presented show that elevated glucose (25 mM) up-regulates IGFBP-2 expression and secretion. In moderately elevated glucose (15 mM) levels, leptin (12.5 nM) up-regulates the expression and secretion of IGFBP-2 in MCF-7 breast cancer cells. There were no significant differences in cell proliferation between the groups. Conclusion: This study shows for the first time that elevated glucose levels up-regulate IGFBP-2 in breast cancer cells and that elevated glucose facilitates the cell response to leptin treatment, which results in an increase of IGFBP-2 levels. This pilot study is the first step in revealing the interactions between glucose levels, leptin and IGFBP-2 and provides the base for further investigations into the obesity and cancer link.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Smit, S.G. Sicco |
| Supervisor name: | Russo, Dr. V.C. and Murdoch Childrens Research Institute, Melbourne |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 11:05 |
| Last Modified: | 25 Jun 2020 11:05 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2510 |
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