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  • Original Paper
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Opposite transcriptional activity between the wild type c-myc gene coding for c-Myc1 and c-Myc2 proteins and c-Myc1 and c-Myc2 separately

Oncogene volume 18, pages 5662–5671 (1999)Cite this article

Abstract

E-cadherin expression was previously shown to be activated by RB and c-myc specifically in epithelial cells, through interaction with the AP-2 transcription factor. Here we show that only a wild type c-myc gene, coding for the two c-Myc proteins c-Myc2 and c-Myc1, was able to transactivate the E-cadherin promoter, in contrast to c-Myc2 or c-Myc1 alone which strongly repressed E-cadherin in both epithelial cells and fibroblasts. In addition, overexpression of c-myc2 or c-myc1 inhibited c-myc and RB-mediated activation in a dose-dependent manner, suggesting that the ratio of the two c-Myc proteins is essential for transactivation. We also showed by using several mutants of the E-cadherin promoter, that the AP-2 binding sites were the main target of c-myc2- and c-myc1-mediated repression. AP-2-mediated inhibition was cell-type specific, as was the activation. Nevertheless, when high amounts of c-myc2 and c-myc1 were used, a second c-myc-mediated repression was observed, possibly mediated by the Inr sequence of the E-cadherin promoter. However, this repression was independent of cell type. Our results suggest a new way to regulate c-myc transcriptional activity by interfering with the ratio of the two c-myc proteins, which has already been found to be disrupted in vivo in several tumor types.

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Acknowledgements

We are very grateful to S Hann for the CMV c-myc1, CMV c-myc2 and (EMS)4CAT constructs, to B Eisenman and to E Blackwood for c-myc mut3 and mut15, to E Ziff and F Tronche for the C/EBPα and Albumin promoters. We thank F Besançon for critical reading of the manuscript. This work was supported by grants from Association pour la Recherche sur le Cancer (no. 6256), the Fondation pour la Recherche Médicale and the GEFLUC. E Batsché was supported by predoctoral fellowships from La Ligue contre le Cancer and from La Fondation pour la Recherche Médicale.

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  1. CJF INSERM 94-02, Université René Descartes, 45 rue des Saints-Pères, Paris, 75270, Cedex 06, France

    Eric Batsché & Chantal Crémisi

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  1. Eric Batsché
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Batsché, E., Crémisi, C. Opposite transcriptional activity between the wild type c-myc gene coding for c-Myc1 and c-Myc2 proteins and c-Myc1 and c-Myc2 separately. Oncogene 18, 5662–5671 (1999). https://doi.org/10.1038/sj.onc.1202927

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