Leptin is a growth factor for colonic epithelial cells.
OBJECTIVE
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.
Hardwick
J C
JC
Department of Experimental Internal Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. J.C.Hardwick@amc.uva.nl
Van Den Brink
G R
GR
Offerhaus
G J
GJ
Van Deventer
S J
SJ
Peppelenbosch
M P
MP
D000230:Adenocarcinoma / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002352:Carrier Proteins / Q000187:drug effects* / Q000302:isolation & purification; D003110:Colonic Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D020738:Leptin / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D009765:Obesity / Q000150:complications; D011494:Protein Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D006133:Growth Substances; C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; C515447:leptin receptor, mouse; D011494:Protein Kinases; D001973:Bromodeoxyuridine; D013936:Thymidine