Oncogenes conferring metastatic potential induce increased branching of Asn-linked oligosaccharides in rat2 fibroblasts.
Increased -GlcNA beta-6 Man alpha 1-6 Man beta 1- branching of Asn-linked oligosaccharides has been observed in a number of rodent and human tumor cell lines and the structures have been correlated with enhanced metastatic potential of murine tumor cells. Here we have compared the malignant potential and levels of beta 1-6-branched oligosaccharides in rat 2 fibroblast transfected with the cytoplasmic tyrosine kinase v-fps/fes, the activated GTPase T24 H-ras, and the nuclear oncogene c-myc. Rat2 cells transfected with activated c-myc were non-tumorigenic in nude mice and did not show elevated levels of beta 1-6 branched oligosaccarides, whereas transfectants carrying H-ras or v-fps were tumorigenic and generally exhibited metastatic potential which was associated with increased beta 1-6 branching. Enhanced expression of beta 1-6 branched oligosaccharides did not correlate with increased ratios of UDP-HexNAc to UDP-Hex, but was accompanied by elevated GlcNAc-transferase V activity, increased sensitivity of the cells to the toxic effects of leukoagglutinin, and an altered intracellular distribution of beta 1-6-branched oligosaccharides as visualized by fluorescent lectin staining. These results provide information on the quantitative and qualitative relationships between oncogene expression and cellular glycosylation and suggest that the ability of an oncogene to confer metastatic potential may be related to its ability to induce increased branching of Asn-linked oligosaccharides.
Dennis
J W
JW
Division of Cancer and Cell Biology, Mount Sinai Hospital Research Institute, Toronto, Ontario, Canada.
Kosh
K
K
Bryce
D M
DM
Breitman
M L
ML
D000818:Animals; D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006001:Glycoconjugates / Q000032:analysis; D037102:Lectins / Q000378:metabolism; D009362:Neoplasm Metastasis; D009844:Oligosaccharides / Q000032:analysis* / Q000378:metabolism; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000032:analysis; D016283:Proto-Oncogene Proteins p21(ras); D051381:Rats; D014162:Transfection
D006001:Glycoconjugates; D037102:Lectins; D009844:Oligosaccharides; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras)