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A role for atm in E-cadherin-mediated contact inhibition in epithelial cells

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Summary

Ataxia telangiectasia is a hereditary pleiomorphic syndrome caused by loss of Atm, a phosphoprotein involved in multiple signaling pathways. Here, we propose a novel role for atm in cultured epithelial cells, namely the regulation of cell growth by contact inhibition. We show that atm is upregulated in epithelial cells reaching confluence. Conditional expression of the PI 3-Kinase domain of atm in non-confluent Tac-2 epithelial cells increases the expression of the anti-proliferative gene Tis-21 and downregulates key cell cycle regulator genes, such as cyclins A, B1, B2, E and E2. Finally, we demonstrate that upregulation of atm, and thus Tis-21, in confluent Tac-2 cells can be inhibited by an E-cadherin antibody blocking specifically homophilic E-cadherin interactions between adjacent cell surfaces. Altogether, these results suggest that atm could participate in a molecular pathway linking extracellular signalling to cell cycle control and may help further clarify the role of Atm in epithelial cell biology and carcinogenesis.

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Acknowledgments

We thank Y. Shiloh (Tel Aviv University, Israel) for providing the ATM 15-1 clone.

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Authors and Affiliations

  1. Division of Oncology, Geneva Medical School, Geneva 4, Switzerland

    Geneviève Vaudan Vutskits, Laurence Mayor, Philippe Maillet & André-Pascal Sappino

  2. Department of Genetics and Microbiology, Geneva Medical School, Geneva 4, Switzerland

    Patrick Salmon & Christophe Cudré-Mauroux

  3. Department of Anesthesiology, Pharmacology and Intensive Care, University Hospital of Geneva, Geneva 4, Switzerland

    Laszlo Vutskits

  4. Department of Morphology, Geneva Medical School, Geneva 4, Switzerland

    Jesus Soriano & Roberto Montesano

  5. Division of Oncology, Geneva Medical School, 1 rue Michel-Servet, 1211, Geneva 4, Switzerland

    Geneviève Vaudan Vutskits

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  1. Geneviève Vaudan Vutskits
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  2. Patrick Salmon
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  3. Laurence Mayor
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  4. Laszlo Vutskits
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  5. Christophe Cudré-Mauroux
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  6. Jesus Soriano
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  8. Philippe Maillet
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  9. André-Pascal Sappino
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Correspondence to Geneviève Vaudan Vutskits.

Additional information

Financial support: This work was supported by the Swiss National Foundation Grant (Bern, Switzerland) 3100-063553.00/1 to André-Pascal Sappino

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Vutskits, G.V., Salmon, P., Mayor, L. et al. A role for atm in E-cadherin-mediated contact inhibition in epithelial cells. Breast Cancer Res Treat 99, 143–153 (2006). https://doi.org/10.1007/s10549-006-9195-y

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  • DOI: https://doi.org/10.1007/s10549-006-9195-y

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