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ToolsOgunwobi, O. O. and Beales, I. L. P. (2008) Leptin stimulates the proliferation of human oesophageal adenocarcinoma cells via HB-EGF and TGFa mediated transactivation of the epidermal growth factor receptor. British Journal of Biomedical Science, 65 (3). pp. 121-127.
Full text not available from this repository. (Request a copy)Abstract
Obesity increases the risk of developing oesophageal adenocarcinoma (OAC) as well as several other cancers. Leptin is secreted by adipocytes and serum leptin levels rise with body mass index. Leptin stimulates proliferation and inhibits apoptosis in OAC cells but the mechanisms are not fully elucidated, Transactivation of the epidermal growth factor receptor (EGFR) is an important signalling mechanism for G-protein-coupled receptors, but the relationship with leptin-type receptors has not been examined and the authors hypothesise that leptin-induced proliferation involves EGFR signalling. This study examines the effect of leptin on EGFR signalling in cultured cell lines. Leptin stimulated proliferation in four OAC lines expressing leptin receptors (OE33, OE19, BIC-1 and FLO) and this was abolished by specific EGFR inhibitors (PD153035 and AG1478). Leptin-induced proliferation was inhibited by neutralising antibodies to transforming growth factor-α (TGFα and HB-EGF) but not by anti-amphiregulin. Leptin significantly increased gene expression of HB-EGF and TGFα as measured by a quantitative real-time polymerase chain reaction (PCR) method but did not alter amphiregulin and EGFR gene expression. Leptin increased extracellular release of HB-EGF and TGFα and this was blocked by matrix metalloproteinase (MMP) inhibitors. The MMP inhibitors also abolished leptin-induced proliferation as well as leptin-induced EGFR tyrosine phosphorylation, but did not affect proliferation or EGFR activation induced by TGFα. The authors conclude that leptin stimulates OAC proliferation via increased gene expression of HB-EGF and TGFα, MMP-mediated extracellular release of HB-EGF and TGFα and subsequent activation of EGFR.
| Item Type: | Article |
|---|---|
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology |
| Depositing User: | EPrints Services |
| Date Deposited: | 25 Nov 2010 11:11 |
| Last Modified: | 25 Jun 2024 11:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/14309 |
| DOI: | 10.1080/09674845.2008.11732814 |
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