[The role of ERK1/2 in leptin promoting the proliferation of human endometrial cancer cell line Ishikawa].
OBJECTIVE
Epidemiologic studies showed that leptin is closely related to the tumorigenesis of endometrial cancer, but the mechanism is unclear. As a mitogenic agent, leptin can promote the proliferation of many kinds of cells. This study was to explore the role of extracellular signal-regulated kinase 1/2 (ERK1/2) in leptin promoting the proliferation of human endometrial cancer cell line Ishikawa.


METHODS
The expression of leptin receptor OB-Rb in Ishikawa cells was detected by fluoroimmunoassay. Ishikawa cells were treated by leptin at various concentrations (0, 10, 50, 100, and 150 ng/ml) for different time (6, 12, and 24 h). Cell proliferation was examined by MTT assay. Meanwhile, the effect of PD98059, selective inhibitor of ERK1/2, on the proliferation of Ishikawa cells induced by leptin was also studied. Ishikawa cells were treated with 100 ng/ml leptin for different time (20, 40, and 60 min), then the levels of phosphorylated ERK1/2 (p-ERK1/2) and ERK1/2 were examined by Western blot.


RESULTS
Fluoroimmunoassay showed the presence of OB-Rb in Ishikawa cells. Leptin stimulated the proliferation of Ishikawa cells. This effect was maximal at 100 ng/ml after 24-hour treatment, and there was no significant difference between 100 ng/ml group and 150 ng/ml group (P=0.129). Blocking ERK1/2 phosphorylation by PD98059 significantly reduced the proliferation of Ishikawa cells stimulated by leptin. When treated with 100 ng/ml Leptin and 100 micromol/L PD98059 for 24 h, cell proliferation rate was (6.88+/-0.86)%. ERK1/2 phosphorylation was enhanced significantly in Ishikawa cells after treatment of 100 ng/ml leptin.


CONCLUSIONS
Leptin may promote the proliferation of endometrial cancer Ishikawa cells by activating ERK1/2 signaling pathway.
Gong
Cheng
C
Department of Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, PR China.
Liu
Yi
Y
Xiao
Wei
W
Yin
Jie
J
Wang
Dong-Hua
DH
Sheng
Hui
H
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D020738:Leptin / Q000008:administration & dosage / Q000494:pharmacology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation; D054411:Receptors, Leptin / Q000378:metabolism
D005419:Flavonoids; D020738:Leptin; D054411:Receptors, Leptin; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one