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  • Original Paper
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Hepatitis B virus-related insertional mutagenesis implicates SERCA1 gene in the control of apoptosis

Oncogene volume 19, pages 2877–2886 (2000)Cite this article

Abstract

We have used the Hepatitis B Virus DNA genome as a probe to identify genes clonally mutated in vivo, in human liver cancers. In a tumor, HBV-DNA was found to be integrated into the gene encoding Sarco/Endoplasmic Reticulum Calcium ATPase (SERCA), which pumps calcium, an important intracellular messenger for cell viability and growth, from the cytosol to the endoplasmic reticulum. The HBV X gene promoter cis-activates chimeric HBV X/SERCA1 transcripts, with splicing of SERCA1 exon 11, encoding C-terminally truncated SERCA1 proteins. Two chimeric HBV X/SERCA1 proteins accumulate in the tumor and form dimers. In vitro analyses have demonstrated that these proteins localize to the ER, determine its calcium depletion and induce cell death. We have also shown that these biological effects are related to expression of the SERCA, rather than of the viral moiety. This report involves for the first time the expression of mutated SERCA proteins in vivo in a tumor cell proliferation and in vitro in the control of cell viability.

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Acknowledgements

We thank P Champeil for critical reading of the paper and most helpful discussion. This work was supported by grants from INSERM, LNC no 8981 and ARC no 9327 (France). M Chami, D Gozuacik and K Saigo are recipient of fellowships from LNC (France), TUBITAK (Turkey) and FRM (France), respectively.

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Author notes

  1. Mounia Chami, Devrim Gozuacik and Kenichi Saigo: M Chami, D Gozuacik and K Saigo contributed equally to this work

Authors and Affiliations

  1. >U-370 INSERM, Necker Institute, Paris, 75015, France

    Mounia Chami, Devrim Gozuacik, Kenichi Saigo, Christian Bréchot & Patrizia Paterlini-Bréchot

  2. Second Department of Surgery, Chiba University, Chiba, 263-8852, Japan

    Kenichi Saigo & Tetsuro Urashima

  3. U-442 INSERM, Université Paris Sud, Orsay, 91405, France

    Thierry Capiod & Michel Claret

  4. URA CNRS 2096, CEA Saclay, Gif sur Yvette, 91191, France

    Pierre Falson & Marc le Maire

  5. Pasteur Institute, Paris, 75015, France

    Hervé Lecoeur & Marie-Lyse Gougeon

  6. Centre National Génotypage, Evry, 91057, France

    Jack Beckmann

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Chami, M., Gozuacik, D., Saigo, K. et al. Hepatitis B virus-related insertional mutagenesis implicates SERCA1 gene in the control of apoptosis. Oncogene 19, 2877–2886 (2000). https://doi.org/10.1038/sj.onc.1203605

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