title: Enhanced expression of the β4-galactosyltransferase 2 gene impairs mammalian tumor growth.
abstract: Altered N-glycosylation of membrane proteins is associated with malignant transformation of cells. We found that the expression of the β4-galactosyltransferase 2 (β4GalT2) 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 β4GalT2 gene. We isolated a clone, B16-β4GalT2, showing its β4GalT2 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-β4GalT2 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 β4GalT2 gene. To pursue a clinical usefulness of the β4GalT2 gene for suppressing human tumor growth, we injected adenoviruses carrying the human β4GalT2 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 β4GalT2 gene expression in tumors is one of the promising approaches to suppress human tumor growth.
authors.affiliation: 1] Division of Pathology and Cell Therapy, Chiba Cancer Research Institute, Chiba, Chiba, Japan [2] Department of Molecular Biology and Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tagawa
authors.affiliation: Department of Biosignal Research, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Shirane
authors.affiliation: Division of Pathology and Cell Therapy, Chiba Cancer Research Institute, Chiba, Chiba, Japan.
authors.forename: L
authors.initials: L
authors.lastname: Yu
authors.affiliation: 1] Department of Biosignal Research, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan [2] Laboratory of Glycobiology, Department of Bioengineering, Nagaoka University of Technology, Nagaoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sato
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, the University of Tokyo, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Furukawa
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Mizuguchi
authors.affiliation: Laboratory of Glycobiology, Department of Bioengineering, Nagaoka University of Technology, Nagaoka, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Kuji
authors.affiliation: Division of Pathology and Cell Therapy, Chiba Cancer Research Institute, Chiba, Chiba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kawamura
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: 1] Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan [2] Okazaki Institute for Integrative Bioscience and Institute for Molecular Science, National Institutes of Natural Sciences, Okazaki, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Biosignal Research, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hayakawa
authors.affiliation: 1] Department of Biosignal Research, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan [2] Laboratory of Glycobiology, Department of Bioengineering, Nagaoka University of Technology, Nagaoka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Sawada
authors.affiliation: 1] Department of Biosignal Research, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan [2] Laboratory of Glycobiology, Department of Bioengineering, Nagaoka University of Technology, Nagaoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Furukawa
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D005700:Galactosyltransferases / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008546:Melanoma, Experimental / Q000235:genetics* / Q000473:pathology*; D008565:Membrane Proteins / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D014161:Transduction, Genetic
chemical_list: D008565:Membrane Proteins; D005700:Galactosyltransferases; C419407:beta-1,4-galactosyltransferase II