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Cell context reveals a dual role for Maf in oncogenesis

Oncogene volume 25, pages 1299–1310 (2006)Cite this article

Abstract

Maf b-Zip transcription factors are involved in both terminal differentiation and oncogenesis. To investigate this apparent contradiction, we used two different primary cell types and performed an extensive analysis of transformation parameters induced by Maf proteins. We show that MafA and c-Maf are potent oncogenes in chicken embryo fibroblasts, while MafB appears weaker. We also provide the first evidence that MafA can confer growth factor independence and promote cell division at low density. Moreover, using MafA as a model, we identified several parameters that are critical for Maf transforming activities. Indeed, MafA ability to induce anchorage-independent cell growth was sensitive to culture conditions. In addition, the transforming activity of MafA was dependent on its phosphorylation state, since mutation on Ser65 impaired its ability to induce growth at low density and anchorage-independent growth. We next examined transforming activity of large Maf proteins in embryonic neuroretina cells, where they are known to induce differentiation. Unlike v-Jun, MafA, MafB and c-Maf did not show oncogenic activity in these cells. Moreover, they counteracted transformation induced by constitutive activation of the Ras/Raf/MEK pathway. Taken together, our results show that Maf proteins could display antagonistic functions in oncogenesis depending on the cellular context, and support a dual role for Maf as both oncogenes and tumor suppressor-like proteins.

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Acknowledgements

We thank Marc Castellazzi, Makoto Nishizawa, Andy Catling and Joram Piatigorsky for providing reagents used in this study, and Georges Calothy for critical reading of the manuscript. We also thank Marc Castellazzi for helpful discussions. This work was funded by the Centre National de la Recherche Scientifique, the Institut Curie, and by grants from the Ligue Nationale Contre le Cancer (Comité de l'Essonne), the Association pour la Recherche sur le Cancer (grant 3534) and Retina France. KSF was supported by a fellowship from the Association pour la Recherche sur le Cancer. IH was supported by a fellowship from the Ligue Nationale Contre le Cancer (Comité de l'Oise).

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  1. M-P Felder-Schmittbuhl

    Present address: CNRS UMR 7518, Centre de Neurochimie, Strasbourg, France

Authors and Affiliations

  1. Institut Curie, CNRS UMR 146, Centre Universitaire, Laboratoire 110, Orsay Cedex, France

    C Pouponnot, K Sii-Felice, I Hmitou, N Rocques, L Lecoin, S Druillennec, M-P Felder-Schmittbuhl & A Eychène

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  1. C Pouponnot
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Correspondence to C Pouponnot or A Eychène.

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Pouponnot, C., Sii-Felice, K., Hmitou, I. et al. Cell context reveals a dual role for Maf in oncogenesis. Oncogene 25, 1299–1310 (2006). https://doi.org/10.1038/sj.onc.1209171

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