Estradiol Activates MAPK Signaling Pathway By Estrogen Inducing VEGF And BFGF In Endometrial Cancer Cells

Endometrial carcinoma is one of the most common female genitaltract malignancies with increasing morbidity reported worldwide in recent years.It is well-known that risk for endometrial adenocarcinoma increases in patientswith high estrogen levels that are unopposed by progestins, since estrogenexhibits growth-promoting properties in endometrial cancer cells，but thespecific pathogenesis has been no definite conclusion. Unlimited proliferation isone of the main characteristics of tumor cells, and angiogenesis is themain characteristics of tumor, they are closely related to tumor occurrence anddevelopment. Previous study showed that, estradiol can regulate the activity ofNF-k B, may be through the AKT signaling pathway. Estrogen induced theproduction of VEGF, bFGF and IL-8via a mechanism involving activation AKTsignal transmission pathway. Moreover, we try to elucidate the mechanism ofthe activation in two endometrial cancer cell lines, Ishikawa cells withendogenous ER and HEC-1A cells with poor expression of ER with MAPKpathway. Objective: The activation of mitogen-activated proteinkinase(MAPK) signal transduction by estradiol inducing vascularendothelial growth factor(VEGF) and basic fibroblast growth factor(bFGF)mediated both by estrogen receptor in endometrial cancer cells. Methods:Ishikawa and HEC-1A endometrial cells were treated by E2with differentconcentrations, the phosphorylated ERK1/2(p-ERK1/2) and totalERK1/2(ERK1/2) were examined by western blot. Ishikawa and HEC-1Acells were pretreated by BIBF1120, Ponatinib and U0126, the effects onMAPK pathway by E2were analyzed through RT-PCR and western blot.Results: E2can stimulated Ishikawa and HEC-1A cells p-ERK1/2ondifferent concentrations, the maximum p-ERK1/2activated with10-6mol/L.VEGF can be activated by E2in Ishikawa cells but not inHEC-1A cells. MAPK signal transduction can be activated by E2inIshikawa and HEC-1A cells. Both BIBF1120and U0126can inhibit theactivation of MAPK signal transduction by E2in Ishikawa cells, Ponatinibcan inhibit MAPK signal transduction by E2in HEC-1A cells. Conclusions:The activation of signal pathway by E2is not the same in an ER-dependentmanner and ER-independent in HEC-1A cells. The cell functions of estradiol activates MAPK signaling pathway byinducing VEGF and bFGF in endometrial cancer cellsObjective: The activation of mitogen-activated protein kinase(MAPK)signal transduction by estradiol inducing vascular endothelial growthfactor(VEGF) and basic fibroblast growth factor(bFGF) mediated both byestrogen receptor in endometrial cancer cells. Methods: Ishikawa and HEC-1Aendometrial cells were treated after estradiol stimulation, VEGF receptorinhibitor, FGF receptor inhibitor or MAPK pathway inhibitor stimulationfollowed by estradiol. Cell colony formation assay, flow cytometry, migrationand MTT assay were used to examine the proliferation in Ishikawa and HEC-1Acells.Results: The abilities of proliferation and cell cycle were significantlyincreased in Ishikawa and HEC-1A cells after estradiol stimulation, inhibitorgroups were signifi cantly decreased than that in estradiol group. Conclusions:The activation of signal pathway by E2is not the same in an ER-dependentmanner and ER-independent in HEC-1A cells.