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Connexin43 pseudogene is expressed in tumor cells and inhibits growth

Oncogene volume 23, pages 4763–4770 (2004)Cite this article

Abstract

Pseudogenes are classically thought of as nonfunctional DNA sequences due to their inability to be translated, or to produce a functional protein. Gap junctions, a multiprotein complex made of proteins called connexins, are involved in intercellular communication and are deregulated in many cancers. Connexin43 (Cx43) is the only connexin for which a pseudogene has been reported so far. The Cx43 pseudogene (ΨCx43) has all of the features of an expressed gene. We identified the presence of a ΨCx43 mRNA transcript in several cancer cell lines and in none of the normal mammary epithelial cells studied. Using an in vitro translation assay, we found that the ΨCx43 coding plasmid could be translated into a 43 kDa protein. This was further confirmed by expressing a ΨCx43-green fluorescence protein fusion protein in breast cancer MCF-7 cells. We then examined the functional significance of the ΨCx43. In both MTT growth and colony formation assays, significant growth inhibition was observed, a feature common to cells overexpressing the Cx43 gene. However, using a scrape-loading assay, we could not detect any effect on gap junctional intercellular communication. Based on our findings, ΨCx43 joins and enlarges the thus far restricted group of functionally transcribed and translated pseudogenes.

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Acknowledgements

This work was supported by grants from the Canadian Breast Cancer Research Initiative, McGill Center for Translational Research in Cancer & Montreal Breast Cancer Foundation. We are thankful to Dr N Benlimame for her valuable help in microscopy.

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  1. Departments of Oncology, Pharmacology & Therapeutics and Experimental Medicine, Montréal Centre for Experimental Therapeutics in Cancer, Lady Davis Institute for Medical Research, McGill University, Montréal, H3T 1E2, Québec, Canada

    Mustapha Kandouz, Andrew Bier, George D Carystinos, Moulay A Alaoui-Jamali & Gerald Batist

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  1. Mustapha Kandouz
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  2. Andrew Bier
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  3. George D Carystinos
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  4. Moulay A Alaoui-Jamali
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Correspondence to Gerald Batist.

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Kandouz, M., Bier, A., Carystinos, G. et al. Connexin43 pseudogene is expressed in tumor cells and inhibits growth. Oncogene 23, 4763–4770 (2004). https://doi.org/10.1038/sj.onc.1207506

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