Leptin induces mitogenic effect on human choriocarcinoma cell line (JAr) via MAP kinase activation in a glucose-dependent fashion.
Leptin and glucose effect on cell growth has been investigated in the JAr human choriocarcinoma cells. When JAr cells were cultured in the presence of 6m M glucose (LG), proliferation and thymidine incorporation were induced by serum but not by leptin. At variance, at 25m M glucose (HG), proliferation and thymidine incorporation were stimulated by leptin and serum to a comparable extent. HG culturing also enhanced leptin-stimulated insulin receptor substrate 1 (IRS1) and MAPK phosphorylation. Blockage of MAPK activity with PD98059 caused an inhibition of glucose- and leptin-dependent thymidine incorporation. At variance with HG conditions no effects were observed in cells cultured in 6m M glucose upon treatment with PD98059. Neither glucose nor leptin determined a modification in leptin receptors total content. In this study, we provide evidence that in placental cells, leptin, similarly to that observed with insulin, stimulates cell proliferation by inducing the IRS1/MAPK pathway in a glucose-dependent fashion.
Bifulco
G
G
Dipartimento di Ginecologia, Ostetricia e Fisiopatologia della Riproduzione Umana, Naples, Italy. giuseppebifulco@hotmail.com
Trencia
A
A
Caruso
M
M
Tommaselli
G A
GA
Miele
C
C
di Carlo
C
C
Beguinot
F
F
Nappi
C
C
D002455:Cell Division / Q000187:drug effects; D002822:Choriocarcinoma; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D020738:Leptin / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015398:Signal Transduction; D014327:Trophoblasts / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014594:Uterine Neoplasms; D014764:Viral Proteins / Q000378:metabolism
D004338:Drug Combinations; D004791:Enzyme Inhibitors; D005419:Flavonoids; D006133:Growth Substances; D020738:Leptin; C072216:TRS1 protein, Human herpesvirus 5; D014764:Viral Proteins; D004247:DNA; D020928:Mitogen-Activated Protein Kinases; D005947:Glucose; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one