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 β(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.
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Chen, L., Zhang, W., Fregien, N. et al. The her-2/neu oncogene stimulates the transcription of N-acetylglucosaminyltransferase V and expression of its cell surface oligosaccharide products. Oncogene 17, 2087–2093 (1998). https://doi.org/10.1038/sj.onc.1202124
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DOI: https://doi.org/10.1038/sj.onc.1202124
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