• Keqin Hua, Jingxin Din, Qi Cao, Weiwei Feng, Ying Zhang, Liangqin Yao, Yan Huang, Yuqin Zhao, and Youji Feng.
• Department of Gynecology, The Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, PR China. huakeqin@126.com
• Oncol. Rep. 2009 Apr 1;21(4):893-8.

AbstractOur previous study revealed that estrogen regulates nm23-H1 expression thus promoting cell migration-invasion via activating PIK3/Akt pathway. In this study, we explored the effect of hormone on hypoxia-inducible factor-1 (HIF-1alpha), a key factor in cancer invasion and metastasis, via activation of Akt signaling transduction pathway. We treated two ovarian cancer cell lines ES-2 and SKOV3 with 17beta-estradiol, methoxyprogesterone acetate (MPA) only, or hormone combined with and Akt, MAPK pathway inhibitor, or transefected with siRNA targeting Akt sequenced with hormone. Expression of HIF-1alpha was measured by Western blotting. We observed the effect of hormone on nm23-H1 expression after the cells were transfected by siRNA targeting HIF-1alpha or treated with CoCl2 to induce HIF-1alpha overexpression. The 17beta-estradiol increased HIF-1alpha expression in ovarian cancer cells, and this upregulatory effect was abrogated by Akt inhibitor LY294002 (P<0.05) and Akt siRNA interference (P<0.05), but not affected by MAPK inhibitor PD980059 (P>0.05). MPA had the opposite effect. Nm23-H1 protein expression in ES-2 and SKOV3 cells were decreased after treatment with 17beta-estradiol (P<0.05), whereas MPA had the opposite effect. The effect was attenuated by HIF-1alpha siRNA (P<0.05) and enhanced by HIF-1alpha overexpression after CoCl2 treatment (P<0.05). Our data suggest that estrogen and progestin regulate HIF-1alpha expression via Akt signaling pathway, affecting nm23-H1 expression in influencing cell metastasis.

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