Open Access

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
  • View Affiliations

  • 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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December 2017
Volume 38 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

2016 Impact Factor: 2.662
Ranked #31/217 Oncology
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APA
Hao, Y., Zhu, L., Yan, L., Liu, J., Liu, D., Gao, N. ... Lin, B. (2017). c-Fos mediates α1, 2-fucosyltransferase 1 and Lewis y expression in response to TGF-β1 in ovarian cancer. Oncology Reports, 38, 3355-3366. https://doi.org/10.3892/or.2017.6052
MLA
Hao, Y., Zhu, L., Yan, L., Liu, J., Liu, D., Gao, N., Tan, M., Gao, S., Lin, B."c-Fos mediates α1, 2-fucosyltransferase 1 and Lewis y expression in response to TGF-β1 in ovarian cancer". Oncology Reports 38.6 (2017): 3355-3366.
Chicago
Hao, Y., Zhu, L., Yan, L., Liu, J., Liu, D., Gao, N., Tan, M., Gao, S., Lin, B."c-Fos mediates α1, 2-fucosyltransferase 1 and Lewis y expression in response to TGF-β1 in ovarian cancer". Oncology Reports 38, no. 6 (2017): 3355-3366. https://doi.org/10.3892/or.2017.6052