title: Down-regulation of beta1,4-galactosyltransferase V is a critical part of etoposide-induced apoptotic process and could be mediated by decreasing Sp1 levels in human glioma cells.
abstract: beta1,4-Galactosyltransferase V (beta1,4GalT V; EC 2.4.1.38) is considered to be very important in glioma for expressing transformation-related highly branched N-glycans. Recently, we have characterized beta1,4GalT V as a positive growth regulator in several glioma cell lines. However, the role of beta1,4GalT V in glioma therapy has not been clearly reported. In this study, interfering with the expression of beta1,4GalT V by its antisense cDNA in SHG44 human glioma cells markedly promoted apoptosis induced by etoposide and the activation of caspases as well as processing of Bid and expression of Bax and Bak. Conversely, the ectopic expression of beta1,4GalT V attenuated the apoptotic effect of etoposide on SHG44 cells. In addition, both the beta1,4GalT V transcription and the binding of total or membrane glycoprotein with Ricinus communis agglutinin-I (RCA-I) were partially reduced in etoposide-treated SHG44 cells, correlated well with a decreased level of Sp1 that has been identified as an activator of beta1,4GalT V transcription. Collectively, our results suggest that the down-regulation of beta1,4GalT V expression plays an important role in etoposide-induced apoptosis and could be mediated by a decreasing level of Sp1 in SHG44 cells, indicating that inhibitors of beta1,4GalT V may enhance the therapeutic efficiency of etoposide for malignant glioma.
authors.affiliation: Key Laboratory of Medical Molecular Virology, Ministry of Education and Health, Gene Research Center, Shanghai Medical College of Fudan University (formerly Shanghai Medical University), Shanghai 200032, China.
authors.forename: Jianhai
authors.initials: J
authors.lastname: Jiang
authors.forename: Jialin
authors.initials: J
authors.lastname: Shen
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.forename: Yuanyan
authors.initials: Y
authors.lastname: Wei
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Chen
authors.forename: Hongliang
authors.initials: H
authors.lastname: Zong
authors.forename: Si
authors.initials: S
authors.lastname: Zhang
authors.forename: Maoyun
authors.initials: M
authors.lastname: Sun
authors.forename: Jianhui
authors.initials: J
authors.lastname: Xie
authors.forename: Xiangfei
authors.initials: X
authors.lastname: Kong
authors.forename: Yanzhong
authors.initials: Y
authors.lastname: Yang
authors.forename: Aiguo
authors.initials: A
authors.lastname: Shen
authors.forename: Hanzhou
authors.initials: H
authors.lastname: Wang
authors.forename: Jianxin
authors.initials: J
authors.lastname: Gu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D016373:DNA, Antisense / Q000235:genetics; D015536:Down-Regulation; D005047:Etoposide / Q000494:pharmacology*; D005700:Galactosyltransferases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D037121:Plant Lectins / Q000378:metabolism; D011134:Polysaccharides / Q000096:biosynthesis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051023:BH3 Interacting Domain Death Agonist Protein; D016373:DNA, Antisense; D037121:Plant Lectins; D011134:Polysaccharides; D012333:RNA, Messenger; C017707:Ricinus communis agglutinin-1; D016329:Sp1 Transcription Factor; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D005047:Etoposide; D005700:Galactosyltransferases; C419408:beta-1,4-galactosyltransferase V; D020169:Caspases