title: Estrogen induced β-1,4-galactosyltransferase 1 expression regulates proliferation of human breast cancer MCF-7 cells.
abstract: Beta 1,4-galactosyltransferase 1 (B4GALT1) synthesizes galactose β-1,4-N-acetylglucosamine (Galβ1-4GlcNAc) groups on N-linked sugar chains of glycoproteins, which play important roles in many biological events, including the proliferation and migration of cancer cells. A previous microarray study reported that this gene is expressed by estrogen treatment in breast cancer. In this study, we examined the regulatory mechanisms and biological functions of estrogen-induced B4GALT1 expression. Our data showed that estrogen-induced expression of B4GALT1 is localized in intracellular compartments and in the plasma membrane. In addition, B4GALT1 has an enzyme activity involved in the production of the Galβ1-4GlcNAc structure. The result from a promoter assay and chromatin immunoprecipitation revealed that 3 different estrogen response elements (EREs) in the B4GALT1 promoter are critical for responsiveness to estrogen. In addition, the estrogen antagonists ICI 182,780 and ER-α-ERE binding blocker TPBM inhibit the expression of estrogen-induced B4GALT1. However, the inhibition of signal molecules relating to the extra-nuclear pathway, including the G-protein coupled receptors, Ras, and mitogen-activated protein kinases, had no inhibitory effects on B4GALT1 expression. The knock-down of the B4GALT1 gene and the inhibition of membrane B4GALT1 function resulted in the significant inhibition of estrogen-induced proliferation of MCF-7 cells. Considering these results, we propose that estrogen regulates the expression of B4GALT1 through the direct binding of ER-α to ERE and that the expressed B4GALT1 plays a crucial role in the proliferation of MCF-7 cells through its activity as a membrane receptor.
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan, Republic of Korea.
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Choi
authors.forename: Tae-Wook
authors.initials: TW
authors.lastname: Chung
authors.forename: Cheorl-Ho
authors.initials: CH
authors.lastname: Kim
authors.forename: Han-Sol
authors.initials: HS
authors.lastname: Jeong
authors.forename: Myungsoo
authors.initials: M
authors.lastname: Joo
authors.forename: Buhyun
authors.initials: B
authors.lastname: Youn
authors.forename: Ki-Tae
authors.initials: KT
authors.lastname: Ha
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D047628:Estrogen Receptor alpha / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D005700:Galactosyltransferases / Q000096:biosynthesis* / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008969:Molecular Sequence Data; D050436:Regulatory Elements, Transcriptional
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D005700:Galactosyltransferases; C119701:beta-1,4-galactosyltransferase I