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Biochimie. 2014 Dec;107 Pt B:286-92. doi: 10.1016/j.biochi.2014.09.015. Epub 2014 Sep 18.

c-Jun transcriptionally regulates alpha 1, 2-fucosyltransferase 1 (FUT1) in ovarian cancer.

Author information

1
Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, China; Department of Obstetrics and Gynecology, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
2
Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, China.
3
Department of Biostatistics and Epidemiology, School of Public Health, China Medical University, Shenyang 110001, China.
4
Department of Obstetrics and Gynecology, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
5
Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, China. Electronic address: linbei88@hotmail.com.

Abstract

Alpha 1, 2-fucosyltransferase (FUT 1/2) is a rate-limiting enzyme that catalyzes the synthesis of Lewis y, a cell membrane-associated carbohydrate antigen. In human ovarian cancer, the upregulated expression of FUT1 and Lewis y is associated with advanced pathological stages and involved in cell proliferation, migration and invasion. However, the mechanism underlying the upregulation of FUT1 is largely unknown. Here, we identify an AP-1 binding site in FUT1 promoter in ovarian cancer cells. c-Jun promotes FUT1 expression, thereby enhancing Lewis y biosynthesis in various ovarian cancer cell lines. Moreover, EMSA, luciferase activity and ChIP assays demonstrate c-Jun directly interacts with FUT1 promoter. Furthermore, FUT1 mediates c-Jun-induced cell proliferation in ovarian cancer cells. In human ovarian cancer samples, c-Jun overexpression is linked to malignant degree and positively correlated to FUT1 and Lewis y expression. Taken together, c-Jun could transcriptionally modulate FUT1 expression in ovarian cancer, implicating the potential application of c-Jun inhibitors for human ovarian cancer therapy.

KEYWORDS:

FUT1; Lewis y; Ovarian cancer; Transcriptional regulation; c-Jun

PMID:
25239830
DOI:
10.1016/j.biochi.2014.09.015
[Indexed for MEDLINE]

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