RESUMO
Altered N-glycosylation of membrane proteins is associated with malignant transformation of cells. We found that the expression of the ß4-galactosyltransferase 2 (ß4GalT2) gene is decreased markedly during the transformation. Here, we examined whether the tumor growth activity of B16-F10 mouse melanoma cells can be reduced by the enhanced expression of the ß4GalT2 gene. We isolated a clone, B16-ß4GalT2, showing its ß4GalT2 transcript 2.5 times higher than a control clone, B16-mock, by transducing its cDNA, and transplanted them subcutaneously into C57BL/6 mice to examine their tumor growth activity. The results showed that the average size of tumors formed with B16-mock cells is 13.1±0.76 mm, whereas that of tumors formed with B16-ß4GalT2 cells is 5.1±1.13 mm (P<0.01) 2 weeks after transplantation. Immunohistochemical analyses showed that the apoptosis and the suppression of angiogenesis are induced in the tumors upon transduction of the ß4GalT2 gene. To pursue a clinical usefulness of the ß4GalT2 gene for suppressing human tumor growth, we injected adenoviruses carrying the human ß4GalT2 cDNA into HuH-7 human hepatocellular carcinomas developed in severe combined immunodeficient mice, and observed marked growth retardation of the tumors. The enhancement of the ß4GalT2 gene expression in tumors is one of the promising approaches to suppress human tumor growth.