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Connexin 43, but not connexin 32, is mutated at advanced stages of human sporadic colon cancer

Oncogene volume 21, pages 4992–4996 (2002)Cite this article

Abstract

The membrane-spanning connexin proteins form microscopic intercellular channels that directly connect the cytoplasms of adjacent cells and as such have been implicated in maintenance of tissue homeostasis. They are considered to act as tumor suppressors since their function or expression is frequently aberrant in tumor cells. Several mechanisms appear to be involved in this, but irreversible mutational alterations have not yet been proved to be among them. In this study we have demonstrated for the first time that connexin 43 but not connexin 32 is specifically and quite frequently mutated in human colon sporadic adenocarcinomas. All tumor-associated mutations led to a shift of reading frame and were located in the multifunctional carboxyl-terminal domain of the protein. Expression of mutated connexin 43 protein was restricted to invasive structures of tumors. These findings suggest that mutational alterations of connexin 43 are involved in advanced stages of progression of human colon cancer towards malignancy.

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Acknowledgements

We thank Dr J Cheney for editing the manuscript. We also thank Mr A Panchenko and Mr E Feodorov for their help in collection of samples and Dr O Sinilnikova for helpful discussions. This work was supported in part by the Ministry of Public Health of the Russian Federation. MV Dubina was a recipient of an ICRETT fellowship from the International Union Against Cancer (#157, 02.02.2000).

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Authors and Affiliations

  1. Department of Pathophysiology, St. Petersburg State Pavlov Medical University of St. Petersburg, St. Petersburg, Russia

    Michael V Dubina

  2. Department of Surgical Diseases, St. Petersburg State Pavlov Medical University of St. Petersburg, St. Petersburg, Russia

    Nikolay A Iatckii, Dimitrii E Popov & Sergei V Vasil'ev

  3. Unit of Gene–Environment Interactions, International Agency for Research on Cancer, WHO, Lyon, 69372, France

    Vladimir A Krutovskikh

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  1. Michael V Dubina
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  5. Vladimir A Krutovskikh
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Correspondence to Vladimir A Krutovskikh.

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Dubina, M., Iatckii, N., Popov, D. et al. Connexin 43, but not connexin 32, is mutated at advanced stages of human sporadic colon cancer. Oncogene 21, 4992–4996 (2002). https://doi.org/10.1038/sj.onc.1205630

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