Globular adiponectin, acting via adiponectin receptor-1, inhibits leptin-stimulated oesophageal adenocarcinoma cell proliferation.
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.
Ogunwobi
Olorunseun O
OO
Biomedical Research Centre, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, United Kingdom.
Beales
Ian L P
IL
D055372:AMP-Activated Protein Kinases; D000230:Adenocarcinoma / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D052242:Adiponectin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D019319:Okadaic Acid / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011720:Pyrazoles / Q000378:metabolism; D011743:Pyrimidines / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism*
D052242:Adiponectin; D004791:Enzyme Inhibitors; D020738:Leptin; D009097:Multienzyme Complexes; D020033:Protein Isoforms; D011720:Pyrazoles; D011743:Pyrimidines; D054419:Receptors, Adiponectin; C516138:dorsomorphin; D019319:Okadaic Acid; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases