Forkhead-box A1 suppresses the progression of endometrial cancer via crosstalk with estrogen receptor α

Wang,Jingyun; Bao,Wei; Qiu,Meiting; Liao,Yun; Che,Qi; Yang,Tingting; He,Xiaoying; Qiu,Haifeng; Wan,Xiaoping

doi:10.3892/or.2014.2982

Forkhead-box A1 suppresses the progression of endometrial cancer via crosstalk with estrogen receptor α

Authors:
- Jingyun Wang
- Wei Bao
- Meiting Qiu
- Yun Liao
- Qi Che
- Tingting Yang
- Xiaoying He
- Haifeng Qiu
- Xiaoping Wan
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Affiliations: Department of Obstetrics and Gynecology, Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, P.R. China, Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
Published online on: January 20, 2014 https://doi.org/10.3892/or.2014.2982
Pages: 1225-1234

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Abstract

Mechanisms governing the function of Forkhead-box A1 (FOXA1), a member of the FOX class of transcription factors, have been extensively studied. However, little is known about the activities and expression pattern of FOXA1 in endometrial cancer (EC). In the present study, we investigated the level of FOXA1 in multiple human EC cell lines and clinical samples by immunohistochemistry, qRT-PCR and Western blot analysis. FOXA1 overexpression was observed in estrogen receptor (ER)α-positive EC cell lines (P=0.0048). In endometrial tissues, FOXA1 was significantly upregulated in both normal endometrium and well-differentiated endometrial cancer tissues (P<0.001). Functional analyses of FOXA1 were evaluated by MTT, plate colony formation and Transwell assay. The results revealed that forced expression of FOXA1 inhibited EC cell proliferation, whereas FOXA1 depletion promoted cell viability and was associated with tumorigenesis. The nude mouse tumor xenograft assay also confirmed that ablation of FOXA1 expression promoted cell proliferation. Furthermore, we found that knockdown of FOXA1 decreased the expression of ERα, and FOXA1 interacted with this receptor in the EC cell lines. Collectively, these experiments suggest that FOXA1 is a tumor suppressor in EC and has a possible interaction with ERα.

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