Changes in gene expression of β-1,4-galactosyltransferases by malignant transformation

Abstract

One of the characteristic features of tumors and malignantly transformed cells is the increase of highly branched N-linked oligosaccharides. This high branching was shown to be brought about by the increased activity of N-acetylglucosaminyltransferase (GlcNAcT) V that forms the GlcNAcβ1∅6Man outer branch and is associated with tumor metastasis. In spite of the drastic changes in the structures of N-linked oligosaccharides upon malignant transformation, no significant change in β-1,4-galactosyltransferase (β-1,4-GalT) activity was detected. However, Northern blot analysis of β-1,4-GalTs in several cancer cell lines revealed that the gene expression of β-1,4-GalTs changes dramatically: that of β-1,4-GalT V increases and is proportional to that of GlcNAcT V, and that of β-1,4-GalT II decreases, while those of other β-1,4-GalTs were unchanged. Furthermore, β-1,4-GalT V was shown preferentially to galactosylate the GlcNAcβ1∅6Man outer branch. These results indicate that the increased activities not only of GlcNAcT V, but also of β-1,4-GalT V in tumors and malignant cells contribute to the formation of the highly branched N-linked oligosaccharides.