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Overexpression of regenerating islet-derived 1 alpha and 3 alpha genes in human primary liver tumors with β-catenin mutations

Oncogene volume 25, pages 599–608 (2006)Cite this article

Abstract

The Wnt/β-catenin signaling pathway is activated in many human hepatocellular carcinomas (HCC). We tried to identify the genes involved in carcinogenesis and progression of HCC with β-catenin mutations. We used PCR-based subtractive hybridization to compare gene expression between malignant and benign components of a human HCC occurring in pre-existing adenoma activated for β-catenin. Two of the genes identified belong to the Regenerating gene (REG) family. They encode the Regenerating islet-derived 3 alpha (REG3A/HIP/PAP/REG-III) and 1 alpha (REG1A) proteins, both involved in liver and pancreatic regeneration and proliferation. Using siRNA directed against β-catenin, we demonstrated that REG3A is a target of β-catenin signaling in Huh7 hepatoma cells. The upregulation of REG3A and REG1A expression is significantly correlated to the β-catenin status in 42 HCC and 28 hepatoblastomas characterized for their β-catenin status. Thus, we report strong evidence that both genes are downstream targets of the Wnt pathway during liver tumorigenesis.

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Acknowledgements

We are grateful to B Romagnolo for her help for the SSH procedure. We thank P Andreu for in situ hybridization, and F Letourneur and S Bulenger for sequencing and all the members of our team for helpful discussions. We would like to thank C Figarella and JL Iovanna for providing the REG1A antibodies. This work was supported by INSERM, the Comité de Paris de la Ligue Nationale contre le Cancer, the Association pour la Recherche contre le Cancer, the Ministère Délégué à la Recherche (ACI Biologie du Développement et Physiologie Intégrative), the GIS-Institut des Maladies Rares and the Ligue Nationale contre le Cancer.

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Author notes

  1. C Cavard and B Terris: These authors contributed equally to this work.

Authors and Affiliations

  1. Département GDPM, INSERM U-567, CNRS UMR 8104, Institut Cochin, Université Paris 5, Paris, France

    C Cavard, B Terris, G Grimber, V Audard & C Perret

  2. Service d'Anatomie Pathologique, Hôpital Cochin, Université Paris 5, Paris Cedex, France

    B Terris & B Radenen-Bussiere

  3. INSERM U-370, Institut Necker-Pasteur, Université Paris 5, Paris Cedex, France

    L Christa & M-T Simon

  4. Unite d'Oncogenèse et Virologie Moléculaire, INSERM U-579, Institut Pasteur, Paris Cedex, France

    C-A Renard & M-A Buendia

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  1. C Cavard
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  2. B Terris
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Correspondence to C Cavard.

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Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc).

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Cavard, C., Terris, B., Grimber, G. et al. Overexpression of regenerating islet-derived 1 alpha and 3 alpha genes in human primary liver tumors with β-catenin mutations. Oncogene 25, 599–608 (2006). https://doi.org/10.1038/sj.onc.1208860

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