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

c-Fos mediates α1, 2-fucosyltransferase 1 and Lewis y expression in response to TGF-β1 in ovarian cancer. Oncol Rep. 2017 Dec;38(6):3355-3366 Authors: Hao Y, Zhu L, Yan L, Liu J, Liu D, Gao N, Tan M, Gao S, Lin B 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 pharmac...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research