Leptin Is a Growth Factor for Colonic Epithelial Cells

Gastroenterology. 2001 Jul;121(1):79-90. doi: 10.1053/gast.2001.25490.

Abstract

Background and aims: Obesity increases the risk of colon cancer, whereas physical activity reduces the risk. Plasma levels of leptin increase in proportion to the level of obesity and are reduced by physical activity. Leptin acts as a growth factor for several cell types and thus may provide a biological explanation for the observed epidemiological risk factors. The aim of this study was to investigate whether leptin is a growth factor for colonic epithelial cells.

Methods: The presence of the leptin receptor in human colon cancer cell lines was assessed using reverse-transcription polymerase chain reaction and immunoblotting, and its presence in human colonic tissue was assessed by immunohistochemistry. The effects of leptin in vitro on HT29 cells were assessed by assessing p42/44 mitogen-activated protein kinase phosphorylation, thymidine incorporation, and cell numbers and in vivo in C57BL/6 mice by colonic bromodeoxyuridine incorporation.

Results: The leptin receptor is expressed in human colon cancer cell lines and human colonic tissue. Stimulation with leptin leads to phosphorylation of p42/44 mitogen-activated protein kinase and increases proliferation in vitro and in vivo.

Conclusions: Leptin is a growth factor in colonic epithelial cells and one that may provide a biological explanation for the observed associations between obesity, physical activity, and colon cancer.

MeSH terms

  • Adenocarcinoma / etiology
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Animals
  • Bromodeoxyuridine / metabolism
  • Carrier Proteins / drug effects*
  • Carrier Proteins / isolation & purification
  • Colonic Neoplasms / etiology
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology*
  • Epithelium / drug effects
  • Epithelium / metabolism
  • Female
  • Growth Substances / pharmacology
  • Humans
  • Leptin / isolation & purification
  • Leptin / pharmacology*
  • Mice
  • Obesity / complications
  • Protein Kinases / metabolism
  • Receptors, Cell Surface*
  • Receptors, Leptin
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thymidine / metabolism
  • Tumor Cells, Cultured

Substances

  • Carrier Proteins
  • Growth Substances
  • Leptin
  • Receptors, Cell Surface
  • Receptors, Leptin
  • leptin receptor, human
  • leptin receptor, mouse
  • Protein Kinases
  • Bromodeoxyuridine
  • Thymidine