Virchows Archiv

, Volume 451, Issue 4, pp 771–779

MAD1 (mitotic arrest deficiency 1) is a candidate for a tumor suppressor gene in human stomach

Authors

    • Division of Molecular Genetics and Biofunction, Department of Biomedical Science, Graduate School of MedicineTottori University
    • Division of Organ Pathology, Department of Microbiology and Pathology, Faculty of MedicineTottori University
  • Toshiaki Inoue
    • Division of Human Genome Science, Department of Molecular and Cellular Biology, Faculty of MedicineTottori University
  • Shigeyuki Yamaguchi
    • Division of Molecular Genetics and Biofunction, Department of Biomedical Science, Graduate School of MedicineTottori University
    • Division of Human Genome Science, Department of Molecular and Cellular Biology, Faculty of MedicineTottori University
  • Aiko Inaba
    • Division of Organ Pathology, Department of Microbiology and Pathology, Faculty of MedicineTottori University
  • Naruo Tokuyasu
    • Division of Organ Pathology, Department of Microbiology and Pathology, Faculty of MedicineTottori University
  • Kuan-Teh Jeang
    • Molecular Virology Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious DiseasesNational Institute of Health
  • Mitsuo Oshimura
    • Division of Molecular Genetics and Biofunction, Department of Biomedical Science, Graduate School of MedicineTottori University
  • Hisao Ito
    • Division of Organ Pathology, Department of Microbiology and Pathology, Faculty of MedicineTottori University
Original Article

DOI: 10.1007/s00428-007-0470-z

Cite this article as:
Osaki, M., Inoue, T., Yamaguchi, S. et al. Virchows Arch (2007) 451: 771. doi:10.1007/s00428-007-0470-z

Abstract

Mitotic arrest deficiency 1 (MAD1) is a component of the spindle checkpoint factors that monitor fidelity of chromosomal segregation. We previously confirmed that the level of MAD1 protein was decreased in gastric carcinoma compared with non-tumoral mucosa by conducting proteome-based analyses (Nishigaki R, Osaki M, Hiratsuka M, Toda T, Murakami K, Jeang KT, Ito H, Inoue T, Oshimura M, Proteomics 5:3205–3213, 29). In this study, an immunohistochemical analysis was performed to examine MAD1 expression histologically in gastric mucosa and tumor. MAD1 was detected in the supranuclear portion of normal epithelial, intestinal metaplasia, and adenoma cells, but its expression was not restricted to any specific area in carcinoma cells. Lower levels of expression were noted in 16 (47.1%) of 34 adenomas and in 52 (60.5%) of 86 carcinomas, whereas all normal mucosae and intestinal metaplasias were grouped into cases with higher level of expression. Moreover, the expression of MAD1 was significantly lower in advanced carcinomas than early carcinomas and in intestinal than diffuse type, respectively (P < 0.05). Exogenous expression of wild-type MAD1, but not the mutant MAD1, inhibited cell proliferation and resulted in G2/M accumulation in MKN-1, a gastric carcinoma cell line. Taken together, our findings suggest that the MAD1 gene could be a candidate tumor suppressor gene and that down-regulation of MAD1 expression contribute to tumorigenesis in human stomach.

Keywords

MAD1Gastric carcinomaTumor suppressor geneImmunohistochemistryCentrosome

Copyright information

© Springer-Verlag 2007