okadaic-acid and dorsomorphin

Obesity increases the risk of developing several cancers including oesophageal adenocarcinoma (OAC). Obesity is characterised by hyperleptinaemia and hypoadiponectinaemia: we have hypothesised that these hormonal factors may contribute to the progression of OAC. We have examined the effects of leptin and adiponectin on proliferation of OAC cells. Leptin-stimulated proliferation in four different OAC lines (OE33, OE19, BIC-1 and FLO) and this was inhibited by globular but not full length adiponectin. All four OAC lines expressed both adiponectin-receptor isoforms (AdipoR1 and AdipoR2). Globular adiponectin also inhibited leptin-induced proliferation in rat IEC-18 cells which only expressed AdipoR1. Specific inhibitors of 5'-AMP-activated protein kinase (Compound C) and serine/threonine phosphatases (okadaic acid) and a specific siRNA to AdipoR1 blocked the anti-proliferative effects of adiponectin. Adiponectin inhibited leptin-induced Akt phosphorylation; this action was sensitive to okadaic acid but not to Compound C. Adiponectin deficiency may contribute to the promotion of OAC in obesity.

Topics: Adenocarcinoma; Adiponectin; AMP-Activated Protein Kinases; Animals; Cell Line, Tumor; Cell Proliferation; Enzyme Activation; Enzyme Inhibitors; Esophageal Neoplasms; Humans; Leptin; Multienzyme Complexes; Obesity; Okadaic Acid; Protein Isoforms; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins c-akt; Pyrazoles; Pyrimidines; Rats; Receptors, Adiponectin; RNA Interference