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  • Original Paper
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Loss of expression of the candidate tumor suppressor gene ZAC in breast cancer cell lines and primary tumors

Oncogene volume 18, pages 3979–3988 (1999)Cite this article

Abstract

Loss of chromosome 6q21-qter is the second most frequent loss of chromosomal material in sporadic breast neoplasms suggesting the presence of at least one tumor suppressor gene on 6q. We recently isolated a cDNA encoding a new zinc finger protein which we named ZAC according to its functional properties, namely induction of apoptosis and control of cell cycle progression. ZAC is expressed in normal mammary gland and maps to 6q24-q25, a recognized breast cancer hot spot on 6q. In the present report, we investigated the possible inactivation of ZAC in breast cancer cell lines and primary tumors. We detected no mutation in ZAC coding region in a panel of 45 breast tumors with allelic imbalance of 6q24-q25. However, a survey of eight breast cancer cell lines showed a deeply reduced (three cell lines) or complete loss of (five cell lines) ZAC expression. Treatment of three of these cell lines with the methylation-interfering agent 5-azacytidine induced ZAC re-expression. In addition, Northern blot and RNase protection assay analysis of ZAC expression in 23 unselected primary breast tumors showed a reduced expression in several samples. Together with its functional properties and chromosomal localization, these findings substantiate ZAC as a good candidate for the tumor suppressor gene on 6q24-q25.

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Acknowledgements

We gratefully acknowledge the gifts of mammoplasty reduction tissues by Dr J-P Reynaud, total RNA from hMEC grown in vitro by Dr P Yaswen and MDA-MB-231 cell line by Dr F Vignon. We are grateful to Laurent Charvet for preparation of artwork. B Bilanges is a recipient of a predoctoral fellowship from the Ministère de l'Education Nationale, de la Recherche et de la Technologie. E Basyuk is a recipient of a postdoctoral fellowship from the Ministère des Affaires Etrangères. A Mazumdar is a recipient of postdoctoral fellowships from la Fondation pour la Recherche Médicale and l'Association pour la Recherche contre le Cancer. D Spengler was supported by grant Sp 386/3-1 from the Deutsche Forschungsgemeinschaft. This work was supported by grant ACC-SV4/9504087 from the Ministère de l'Education Nationale, de la Recherche et de la Technologie, grants from the Centre Nationale de la Recherche Scientifique, La Ligue Nationale contre le Cancer and L'Association pour la Recherche contre le Cancer.

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Authors and Affiliations

  1. UPR 9023 CNRS, Mécanismes Moléculaires des Communications Cellulaires, CCIPE, 141 rue de la cardonille, Montpellier, Cedex 05, 34094, France

    Benoit Bilanges, Annie Varrault, Eugenia Basyuk, Abhijit Mazumdar, Colette Pantaloni, Joël Bockaert, Dietmar Spengler & Laurent Journot

  2. Equipe Génome et Cancer, UMR 5535 CNRS, Centre de Recherche CRLC Val d'Aurelle/Paul Lamarque, 34098, Montpellier, Cedex 05, France

    Carmen Rodriguez & Charles Theillet

  3. Max Planck Institute of Psychiatry, Molecular Neurobiology, Kraepelinstrasse, 2-10, Munich, 80804, Germany

    Dietmar Spengler

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Bilanges, B., Varrault, A., Basyuk, E. et al. Loss of expression of the candidate tumor suppressor gene ZAC in breast cancer cell lines and primary tumors. Oncogene 18, 3979–3988 (1999). https://doi.org/10.1038/sj.onc.1202933

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