Leptin stimulates the proliferation of human oesophageal adenocarcinoma cells via HB-EGF and TGF α mediated transactivation of the epidermal growth factor receptor.

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. PMID: 29443659 [PubMed]
Source: British Journal of Biomedical Science - Category: Laboratory Medicine Tags: Br J Biomed Sci Source Type: research