Oncotarget

Research Papers:

FKBP51 decreases cell proliferation and increases progestin sensitivity of human endometrial adenocarcinomas by inhibiting Akt

Jing Dong, Yulian Jiao, Wenli Mu, Bingru Lu, Muyun Wei, Linying Sun, Shengnan Hu, Bin Cui, Xiaowen Liu, Zijiang Chen and Yueran Zhao _

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Oncotarget. 2017; 8:80405-80415. https://doi.org/10.18632/oncotarget.18903

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Abstract

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

Correspondence to:

Yueran Zhao, email: yrzhao@sdu.edu.cn

Keywords: Akt, endometrial adenocarcinoma, FKBP51, progestin sensitivity, proliferation

Received: January 21, 2017     Accepted: June 15, 2017     Published: June 30, 2017

ABSTRACT

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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