Globular adiponectin, acting via adiponectin receptor-1, inhibits leptin-stimulated oesophageal adenocarcinoma cell proliferation

Mol Cell Endocrinol. 2008 Mar 26;285(1-2):43-50. doi: 10.1016/j.mce.2008.01.023. Epub 2008 Feb 7.

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