|Budget Amount *help
¥3,300,000 (Direct Cost : ¥3,300,000)
Fiscal Year 1999 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1998 : ¥2,200,000 (Direct Cost : ¥2,200,000)
Mammalian cells are now shown to contain several β-1、4-galactosyltransferases (β-1,4-GalTs) which are involved in the biosynthesis of glycoprotein. When cells are transformed, they express the highly branched sugar chains with tumor-associated carbohydrate antigens on proteins which are critical to tumorigenicity and metastasis of the cell. During transformation, the gene expression levels of β-1,4-GalTs I, III, IV and VI were not changed while that of β-1,4-GalT II decreased and that of β-1,4-GalT V increased. In order to investigate biological significance of the carbohydrates formed by β-1,4-GalT II and V, their genes were introduced into several cell lines. When β-1,4-GalT II-sense cDNA or β-1,4-GalT V-antisense cDNA was transfected into mouse melanoma F10 cells, altered glycosylation of the membrane glycoproteins was detected by lectin blot analysis. The cells were inoculated into C57B mouse and the ability to form tumors were examined. Mouse melanoma F10 cells formed tumors in the animals while those transfected with β-1,4-Galt II-sense cDNA or β-1,4-GalT V-antisense cDNA failed or developed tumors very slowly. These results indicated that the sugar chains synthesized by β-1,4-GalTs II and V are involved in the growth control mechanism of cells. Further studies are necessary to identify which carbohydrate structures are really engaged in this biological event.