title: HSF1 and Sp1 regulate FUT4 gene expression and cell proliferation in breast cancer cells.
abstract: Lewis Y (LeY) is a carbohydrate tumor-associated antigen. The majority of cancer cells derived from epithelial tissues express LeY type difucosylated oligosaccharides. Fucosyltransferase IV (FUT4) is an essential enzyme that catalyzes the synthesis of LeY oligosaccharides. In a previous study we reported that FUT4 is associated with cell proliferation; however, despite the important role of FUT4 in cancer proliferation and apoptosis, little is known about the mechanisms underlying the regulation of FUT4 transcription. In the current study we investigated the regulation of FUT4 transcription in human breast cancer. We compared the regulation of human FUT4 gene transcription in human breast cancer cells (MCF-7 and MDA-MB-231) using promoter/luciferase analyses. Using a series of promoter deletion constructs, we identified a potential regulatory site located between 0.8 and 1.6 kb of the FUT4 promoter. As shown by EMSA and ChIP analyses, heat-shock factor 1 (HSF1) and Sp1are required for FUT4 promoter activity. In addition, we explored the role of HSF1 and Sp1 on cell proliferation, and found that the ERK1/2 MAPK and PI3K/Akt signaling pathways regulate the expression of FUT4, which play a role in cell proliferation via HSF1 and Sp1. These results suggest that FUT4 is a target gene for HSF1 and Sp1 that is required for cell cycle progression in breast cancer epithelial cells.
authors: Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian, People's Republic of, China.
authors: Xuesong
authors: X
authors: Yang
authors: Jiao
authors: J
authors: Wang
authors: Shuiai
authors: S
authors: Liu
authors: Qiu
authors: Q
authors: Yan
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D000076249:Heat Shock Transcription Factors; D006801:Humans; D016256:Lewis X Antigen / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D016256:Lewis X Antigen; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; C066693:FUT4 protein, human; D005647:Fucosyltransferases; D051057:Proto-Oncogene Proteins c-akt
keywords: BREAST CANCER; FUCOSYLTRANSFERASE IV; HSF1; SIGNALING PATHWAY; Sp1