Analysis of the role of MPA as a molecular-targeted therapy in endometrial cancer.

本研究的目的是评估MPA在调节肿瘤进展中的作用。MPA对1型子宫内膜癌细胞株ERK和Akt均无激活作用，而对2型子宫内膜癌细胞株ERK和Akt均有磷酸化作用。有趣的是，雌二醇（E2）激活ERK和Akt在这两种细胞系。因此，E2的膜受体GPR 30可能是1型和2型子宫内膜癌肿瘤进展的关键分子。GPR 30的激活通过上调细胞周期蛋白D1（cyclin D1）的表达而与肿瘤的增殖密切相关，而上皮间质转化（epithelial-mesenchymal-transition，EMT）是肿瘤侵袭转移的重要环节。我们的数据表明，E-钙粘蛋白和Snail和Slug的核表达减少对子宫内膜癌的预后有影响。因此，阐明和调控EMT信号通路是子宫内膜癌的一种有希望的分子靶向治疗方法。

The aims of our study were to evaluate the role of MPA for the regulation of tumor progression. In type 1 endometrial cancer cell line, MPA did not activate both ERK and Akt, However, ERK and Akt were phosphorylated by MPA in type 2 cell line. Interestingly, estradiol(E2) activated ERK and Akt in both cell lines. Therefore, GPR30, a membrane receptor for E2, might be a key molecule for tumor progression in both type 1 and type 2 endometrial cancers. The activation of GPR30 was associated to tumor proliferation via up regulation of cyclin D1.Furthermore, epithelial-mesenchymal-transition(EMT) is recently identified as an important step in the invasion and metastasis of cancer. Our data indicate that reduced E-cadherin and nuclear expression of Snail and Slug have a prognostic impact in endometrial cancer. Therefore, to clarify and control of EMT signaling is a promising molecular targeting therapy in endometrial cancer.