Leptin is a growth factor for colonic epithelial cells

James C H Hardwick, Gijs R. Van Den Brink, G. J. Offerhaus, Sander J H Van Deventer, Maikel P. Peppelenbosch

Research output: Contribution to journalArticle

Abstract

Background & 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.

Original languageEnglish (US)
Pages (from-to)79-90
Number of pages12
JournalGastroenterology
Volume121
Issue number1
StatePublished - 2001
Externally publishedYes

ASJC Scopus subject areas

  • Gastroenterology

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    Hardwick, J. C. H., Van Den Brink, G. R., Offerhaus, G. J., Van Deventer, S. J. H., & Peppelenbosch, M. P. (2001). Leptin is a growth factor for colonic epithelial cells. Gastroenterology, 121(1), 79-90.