Journal of Membrane Biology

, Volume 218, Issue 1–3, pp 101–106

Both Early and Late Stages of Hepatocarcinogenesis Are Enhanced in Cx32 Dominant Negative Mutant Transgenic Rats with Disrupted Gap Junctional Intercellular Communication

  • Naomi Hokaiwado
  • Makoto Asamoto
  • Mitsuru Futakuchi
  • Kumiko Ogawa
  • Satoru Takahashi
  • Tomoyuki Shirai
Article

Abstract

Connexins are a family of transmembrane proteins essential for the gap junctions, which mediate cell-to-cell communication. Several connexins are reported to be tumor suppressors, and we have established transgenic (Tg) rats with a connexin 32 (Cx32) dominant negative mutant showing high sensitivity to early-stage diethylnitrosamine (DEN)-induced liver carcinogenesis. In this study, we carried out two independent experiments using Tg rats to further investigate the roles of disrupted Cx32 in late-stage carcinogenesis (carcinoma induction and metastasis) in the liver. In the first experiment, of 50 weeks’ duration, DEN was administered at 6 weeks of age and at 26 weeks to explore the effects of carcinogen treatments at different stages. The number of hepatocellular carcinomas (HCCs) was significantly increased in Tg compared with non-Tg rats. The second experiment focused on the effects of Cx32 disruption on metastasis by HCCs induced by administration of DEN and N-nitrosomorpholine. Only Tg rats had multiple metastases of HCCs in the lung, and the development and growth of HCCs was dramatically accelerated in Tg compared to non-Tg rats. Thus, normal function of Cx32 may be essential for suppression of both early and late stages of hepatocarcinogenesis.

Keywords

Gap junction Connexin 32 Transgenic rat Liver Tumor progression 

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Naomi Hokaiwado
    • 1
  • Makoto Asamoto
    • 1
  • Mitsuru Futakuchi
    • 1
  • Kumiko Ogawa
    • 1
  • Satoru Takahashi
    • 1
  • Tomoyuki Shirai
    • 1
  1. 1.Department of Experimental Pathology and Tumor BiologyNagoya City University Graduate School of Medical SciencesNagoyaJapan

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