Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
AMP-Activated Protein Kinases
-
Adenocarcinoma* / etiology
-
Adenocarcinoma* / metabolism
-
Adenocarcinoma* / pathology
-
Adiponectin / chemistry
-
Adiponectin / genetics
-
Adiponectin / metabolism*
-
Animals
-
Cell Line, Tumor
-
Cell Proliferation*
-
Enzyme Activation
-
Enzyme Inhibitors / metabolism
-
Esophageal Neoplasms* / etiology
-
Esophageal Neoplasms* / metabolism
-
Esophageal Neoplasms* / pathology
-
Humans
-
Leptin / metabolism*
-
Multienzyme Complexes / antagonists & inhibitors
-
Multienzyme Complexes / metabolism
-
Obesity* / complications
-
Obesity* / metabolism
-
Obesity* / physiopathology
-
Okadaic Acid / metabolism
-
Protein Isoforms / chemistry
-
Protein Isoforms / genetics
-
Protein Isoforms / metabolism
-
Protein Serine-Threonine Kinases / antagonists & inhibitors
-
Protein Serine-Threonine Kinases / metabolism
-
Proto-Oncogene Proteins c-akt / metabolism
-
Pyrazoles / metabolism
-
Pyrimidines / metabolism
-
RNA Interference
-
Rats
-
Receptors, Adiponectin / genetics
-
Receptors, Adiponectin / metabolism*
Substances
-
Adiponectin
-
Enzyme Inhibitors
-
Leptin
-
Multienzyme Complexes
-
Protein Isoforms
-
Pyrazoles
-
Pyrimidines
-
Receptors, Adiponectin
-
dorsomorphin
-
Okadaic Acid
-
Protein Serine-Threonine Kinases
-
Proto-Oncogene Proteins c-akt
-
AMP-Activated Protein Kinases