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The v-erbA oncogene blocks expression of α2/β1 integrin a normal inhibitor of erythroid progenitor proliferation

Oncogene volume 21, pages 2864–2872 (2002)Cite this article

Abstract

T2EC are chicken erythrocytic progenitors that balance between self-renewal and differentiation as a function of response to specific growth factors. Their transformation by the v-erbA oncogene locks them into the self-renewal program. We show here that the expression of the VLA-2 integrin α2 subunit mRNA is downregulated by v-erbA and that VLA-2 engagement and clustering, brought about by treatment with an α2-specific antibody or by culture on the VLA-2 ligand collagen I, inhibits T2EC proliferation. From competition studies using antibodies, VLA-2 was shown to be involved in the collagen-induced response. While engagement of VLA-2 inhibited proliferation, it was not sufficient to induce differentiation. The transformation of T2EC by v-erbA decreased their interaction with collagen I and the VLA-2 brake on cell proliferation, which may account for the increased proliferation potential of transformed erythrocytic progenitors and for their shedding into the blood of infected chickens. Our data suggest that the interaction between erythroid progenitors and collagen, mediated by VLA-2, play a major role in the control of erythropoiesis in vitro and that this pathway is a target of the v-erbA oncogene.

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Acknowledgements

We are very grateful to Dr Patricia Rousselle for advice in adhesion assays, to Dr Gordon Cann for isolation of the chicken α2 clone, to Prof Martin Pfaff for critical reading of this manuscript and to Bérengère Dalmais for technical assistance. Anne Mey was supported by a fellowship from La Ligue Nationale Contre le Cancer. This work was supported by grants from the Association pour la Recherche sur le Cancer and from the Région Rhône-Alpes to Jacques Samarut (grant # H09873.08.12) and from the National Eye Institute of the National Institutes of Health to Dennis O Clegg (grant # EY 09736).

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Authors and Affiliations

  1. Laboratoire de Biologie Moléculaire et Cellulaire, CNRS UMR 5665, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, Lyon, 69008, France

    Anne Mey & Jacques Samarut

  2. Centre de Génétique Moléculaire et Cellulaire, CNRS UMR 5534, Université Claude Bernard Lyon I, Bat 741, 43 bd du 11 Novembre 1918, 69622 Villeurbanne Cedex, France

    Olivier Gandrillon

  3. Biomedical Research Centre, 2222 Health Sciences Mall, Dept. of Medical Genetics, University of British Columbia, Vancouver, B.C., V6T 1Z3, Canada

    Kelly M McNagny

  4. Neuroscience Research Institute and Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, 93106, California, CA, USA

    Dennis O Clegg

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  1. Anne Mey
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  2. Olivier Gandrillon
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  4. Dennis O Clegg
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  5. Jacques Samarut
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Correspondence to Jacques Samarut.

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Mey, A., Gandrillon, O., McNagny, K. et al. The v-erbA oncogene blocks expression of α2/β1 integrin a normal inhibitor of erythroid progenitor proliferation. Oncogene 21, 2864–2872 (2002). https://doi.org/10.1038/sj.onc.1205411

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