The Study Of Estrogen Induced The Expressing Of Oncogenic Factor By Activated AKT

Background: Endometrial cancer is a common gynecological malignancy, accounting for 20% to 30% in female genital tumors. With the long global average life expectancy of women and increase of using estrogen replacement therapy etc, the incidence of endometrial cancer has been on increasing, but the exact reason of endometrial cancer remains indefinite. It is now generally considered that"non-progesterone antagonism by prolonged effects of estrogen"is the main cause of endometrial cancer. However, how the estrogen regulate cell proliferation is still unclear.AKT(serine/threonine kinase),as the PI3K downstream target protein,is an important signal transmission protein kinase and also the core of PI3K/AKT signal transduction pathway.Researches discovered that estrogen activated PI3K/AKT protein pathway was by activating ligand-dependent ERα. Estrogen and estrogen receptor can activate AKT by non-genomic pathway, which will directly stimulate NF-KB and then promote the development of endometrial cancer. Objective: Estrogen was induced mRNA expression of the oncogenic factors VEGF, bFGF, and IL-8 in the endometrial cell line HEC-1A in order to investigate the relationgship between estrogen and endometrial cancer, understand its role of tumorigenesis.Method:1,Real-time PCR was detected the expression of mRNA VEGF, bFGF and IL-8 in HEC-1A cells after stimulation with 1×10^-6mol/L estradiol(estradiol group) for 8h or 12h; and with being pretreated with 25×10^-6mol/L AKT inhibitor (AKT inhibitor group) or 1×10^-6mol/L ER inhibitor(ER inhibitor group) for 60min following stimulation with 1×10^-6mol/L estradiol for 8h or 12h as well.2,Western Blot was detected the expression of AKT protein in HEC-1A cells after stimulation with 1×10^-6mol/L estradiol for 15min.Result:1,Real-time PCR showed the expression of VEGF,bFGF, IL-8 mRNA in estradiol group were significantly increased than that in control group (P<0.05); the expression of VEGF, bFGF, IL-8 mRNA in AKT inhibitor group were significantly decreased than that in estradiol group(P<0.05), excepting expression of IL-8 mRNA for 12h (P >0.05); the expression of VEGF, bFGF, IL-8 mRNA in ER inhibitor group were significantly decreased than that in estradiol group(P<0.05), apart from the expression of VEGF mRNA were slightly high in estradiol group for 12h, and expression of IL-8 mRNA for 12h (P >0.05).2,Western Blot showed that p-AKT protein expression in HEC-1A cells after stimulation with 1×10^-6mol/L estradiol for 15min was markedly higher than that in the control group (P<0.05). Conclusion:Estrogen induced the production of oncogenic factor VEGF, bFGF and IL-8 via a mechanism involving activation AKT signal transmission pathway.