c-Fos mediates α1, 2-fucosyltransferase 1 and Lewis y expression in response to TGF-β1 in ovarian cancer

Hao,Yingying; Zhu,Liancheng; Yan,Limei; Liu,Juanjuan; Liu,Dawo; Gao,Na; Tan,Mingzi; Gao,Song; Lin,Bei

doi:10.3892/or.2017.6052

c-Fos mediates α1, 2-fucosyltransferase 1 and Lewis y expression in response to TGF-β1 in ovarian cancer

Authors:
- Yingying Hao
- Liancheng Zhu
- Limei Yan
- Juanjuan Liu
- Dawo Liu
- Na Gao
- Mingzi Tan
- Song Gao
- Bei Lin
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Affiliations: Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang, Liaoning 110004, P.R. China, Department of Obstetrics and Gynecology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
Published online on: October 23, 2017 https://doi.org/10.3892/or.2017.6052
Pages: 3355-3366
Copyright: © Hao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

FUT1 is a key rate-limiting enzyme in the synthesis of Lewis y, a membrane-associated carbohydrate antigen. The aberrant upregulation of FUT1 and Lewis y antigen is related to proliferation, invasion and prognosis in malignant epithelial tumors. A c-Fos/activator protein-1 (AP-1) binding site was found in the FUT1 promoter. However, the mechanisms of transcriptional regulation of FUT1 remain poorly understood. TGF-β1 is positively correlated to Lewis y. In the present study, we investigated the molecular mechanism of FUT1 gene expression in response to TGF-β1. We demonstrated that c-Fos was highly expressed in 77.50% of ovarian epithelial carcinoma cases and was significantly correlated with Lewis y. Using luciferase activity and chromatin immunoprecipitation (ChIP) assay, we further revealed that c-Fos interacted with the FUT1 promoter in ovarian cancer cells and transcriptional capacity of the heterodimer formed by c-Fos and c-Jun was stronger than that of the c-Fos or c-Jun homodimers. Then, we demonstrated that TGF-β1 induced dose-dependent c-Fos expression, which was involved in TGF-β1-induced ovarian cancer cell proliferation. In addition, inhibition of MAPK activation or TGF-β1 receptor by pharmacological agents prevented TGF-β1-induced c-Fos and Lewis y expression. Silencing of c-Fos prevented TGF-β1-induced Lewis y expression. Collectively, the results of these studies demonstrated that TGF-β1 regulated FUT1 and Lewis y expression by activating the MAPK/c-Fos pathway.

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