The her-2/neu oncogene stimulates the transcription of N-acetylglucosaminyltransferase V and expression of its cell surface oligosaccharide products

Lin Chen, Weijie Zhang, Nevis L. Fregien, Michael Pierce

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Malignant transformation is associated with changes in the glycosylation of cell surface proteins. For example, the N-linked oligosaccharides containing the [GlcNAcβ(1,6)Man] branch are increased after transformation of many cell types by a number of tumor viruses and oncogenes which induce the expression of N-acetylglucosaminyl-transferase V (GlcNAc-T V), the enzyme that adds this branch. A large percentage of human breast carcinomas have increased N-linked P(1,6) branches on glycoproteins, while up to 30% of breast carcinomas have amplified the oncogene her-2/neu (erb-B2). We tested the hypothesis that expression of her-2/neu stimulates GlcNAc-T V gene expression and increases the β(1,6) branching of N-linked oligosaccharides. We found that neu-transformed NIH3T3 cells have a threefold increase in GlcNAc-T V enzyme activity and increased β(1,6) branching on a specific set of glycoproteins. Promoter/reporter experiments showed that her-2/neu stimulates transcription from the human GlcNAc-T V promoter and that the her-2/neu response element was located about 400 bp 5' of the transcription initiation site and includes three Ets transcription factor binding sequences. Co-transfections with dominant-negative Raf and Ets expression plasmids demonstrated that the transcriptional activation of the GlcNAc-T V promoter by neu is mediated by the Ras-Raf-Ets signal transduction pathway.

Original languageEnglish
Pages (from-to)2087-2093
Number of pages7
JournalOncogene
Volume17
Issue number16
StatePublished - Oct 22 1998

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alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase
Oligosaccharides
Oncogenes
Glycoproteins
Proto-Oncogene Proteins c-ets
Breast Neoplasms
Oncogenic Viruses
Transcription Initiation Site
Response Elements
Enzymes
Glycosylation
Transcriptional Activation
Transfection
Signal Transduction
Membrane Proteins
Plasmids
Cell Count
Gene Expression

Keywords

  • Glycosylation
  • Glycosyltransferase
  • neu/her-2
  • Oncogene

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

The her-2/neu oncogene stimulates the transcription of N-acetylglucosaminyltransferase V and expression of its cell surface oligosaccharide products. / Chen, Lin; Zhang, Weijie; Fregien, Nevis L.; Pierce, Michael.

In: Oncogene, Vol. 17, No. 16, 22.10.1998, p. 2087-2093.

Research output: Contribution to journalArticle

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