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Enhanced expression of the β4-galactosyltransferase 2 gene impairs mammalian tumor growth

Cancer Gene Therapy volume 21, pages 219–227 (2014)Cite this article

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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.

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Acknowledgements

This paper is dedicated to the late Emeritus Professor Hiroshi Terayama in the Zoological Institute, Faculty of Science at the University of Tokyo, who educated and encouraged one of the authors (KF) for many years. We are grateful to Yumi Kobayashi and Kaori Wada at Tokyo Medical and Pharmaceutical College of Technology for their technical assistance. This work was supported by the Grants-in-Aid for Scientific Research (10680696 and 22370048) from the Ministry of Education, Science, Sports, Culture and Technology (MEXT) of Japan, Practical Application Research Fund from Japan Science Technology, and Institutional Grants from Nagaoka University of Technology to KF.

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Authors and Affiliations

  1. Division of Pathology and Cell Therapy, Chiba Cancer Research Institute, Chiba, Chiba, Japan

    M Tagawa, L Yu & K Kawamura

  2. Department of Molecular Biology and Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan

    M Tagawa

  3. Department of Biosignal Research, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan

    K Shirane, T Sato, S Hayakawa, S Sawada & K Furukawa

  4. Department of Bioengineering, Laboratory of Glycobiology, Nagaoka University of Technology, Nagaoka, Japan

    T Sato, R Kuji, S Sawada & K Furukawa

  5. Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, the University of Tokyo, Tokyo, Japan

    S Furukawa

  6. Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan

    H Mizuguchi

  7. Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan

    N Takahashi & K Kato

  8. Okazaki Institute for Integrative Bioscience and Institute for Molecular Science, National Institutes of Natural Sciences, Okazaki, Japan

    K Kato

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  1. M Tagawa
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Correspondence to K Furukawa.

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Current affiliations since the completion of the study: KS, KYORIN Pharmaceutical Co., Ltd., Chiyoda-ku, Tokyo 101-8311, Japan; SS, Research Division, Alist Japan Co., Kobe, Hyogo 651-1513, Japan.

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Tagawa, M., Shirane, K., Yu, L. et al. Enhanced expression of the β4-galactosyltransferase 2 gene impairs mammalian tumor growth. Cancer Gene Ther 21, 219–227 (2014). https://doi.org/10.1038/cgt.2014.21

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