Quantitative analysis for transcriptional alteration of glycosyltransferases in colon cancer

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The type 1 carbohydrate chain,Gal β 1-3GlcNAc,is synthesized by UDP-galactose:β-N-acetylglucoamine β 1,3-galactosyltransferase (β 3Gal-T). Among six β 3Gal-Ts cloned to date, β 3Gal-T5 is an essential enzyme for the synthesis of type 1 chain in epithelium of digestive tracts or pancreatic tissue. It forms the type 1 structure on glycoproteins produced from such tissues. In the present study,we found that the transcriptional regulation for β 3Gal-T5 gene is controlled by homeoproteins, i.e. members of Cdx and hepatocyte nuclear factor (HNF) families. We found an important region (-151~-121 from the transcription initiation site),named the β 3Gal-T5 control element(GCE), for the promoter activity. GCE contained the consensus sequences for members of Cdx and HNF families. Mutations introduced into this sequence abolished the transcriptional activity. Four factors,Cdx1,Cdx2,HNF1 α and HNF1 β,could bind to GCE and transcriptionally activated the β 3Gal-T5 geneTranscriptional regulation of the β3Gal-T5 gene was consistent with that of the members of Cdx and HNF1 families in two in vivo systems,i.e.1) During in vitro differentiation of Caco-2 cells, transcriptional up-regulation of β 3Gal-T5 was observed in correlation with the increase in transcripts for Cdx2 and HNF1 α. 2) Both transcript and protein of β 3Gal-T5 were determined to be significantly down-regulated in cancerous tissue of colon cancer patients. This down-regulation was correlated with the decrease of Cdx1 and HNF1 β expression in cancer tissueThis is the first finding that a glycosyltransferase gene is transcriptionally regulated under control of homeoproteins in a tissue-specific manner. β 3Gal-T5,controlled by the intestinal homeoproteins, may play an important role for the specific function of intestinal cells by modifying the carbohydrate structure of glycoproteins