FKBP51 decreases cell proliferation and increases progestin sensitivity of human endometrial adenocarcinomas by inhibiting Akt
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Jing Dong1, Yulian Jiao1, Wenli Mu1, Bingru Lu1, Muyun Wei1, Linying Sun1, Shengnan Hu1, Bin Cui1, Xiaowen Liu1, Zijiang Chen2 and Yueran Zhao1
1Department of Central Lab, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China
2Reproductive Hospital affiliated to Shandong University, Jinan, Shandong, China
Yueran Zhao, email: email@example.com
Keywords: Akt, endometrial adenocarcinoma, FKBP51, progestin sensitivity, proliferation
Received: January 21, 2017 Accepted: June 15, 2017 Published: June 30, 2017
In this study, we investigated the role of FK506 binding protein 51 (FKBP51) in human endometrial adenocarcinoma progression. Immunohistochemical analysis showed decreased FKBP51 expression in endometrial adenocarcinoma tissues. Moreover, higher FKBP51 expression was observed in the normal secretory phase than in proliferative-phase endometrial tissues. FKBP51-shRNA transfected KLE cells showed high Ser473-phospho Akt with decreased p21 and p27 levels, which promoted S-G2/M phase cell cycle progression and proliferation. Conversely, FKBP51 overexpressing Ishikawa cells showed low Ser473-phospho Akt, which led to increased p21 and p27 levels and, in turn, G0/G1 cell cycle arrest and decreased cell proliferation. FKBP51 overexpression in progesterone receptor-positive Ishikawa cells sensitized them to medroxyprogesterone acetate (MPA; progestin) treatment by repressing Akt signaling. Conversely, FKBP51-shRNA knockdown in RL95-2 cells attenuated progestin sensitivity. These findings indicate FKBP51 inhibits cell proliferation and promotes progestin sensitivity in endometrial adenocarcinoma by decreasing Akt signaling.
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