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Transcription factor ATF3 partially transforms chick embryo fibroblasts by promoting growth factor-independent proliferation

Oncogene volume 20, pages 1135–1141 (2001)Cite this article

Abstract

Activating Transcription Factor 3 (ATF3) is a member of the bZip family of transcription factors. Previous studies in mammalian cells suggested that like other bZip family members e.g. Jun and Fos, ATF3 might play a role in the control of cell proliferation and participate in oncogenic transformation. To investigate this putative ATF3 function directly, the rat ATF3 protein was compared with v-Jun for its ability to transform primary cultures of chick embryo fibroblasts (CEFs). Like CEFs accumulating v-Jun, CEFs accumulating the ATF3 protein displayed a typical, fusiform morphology, associated with an enhanced capacity to grow in medium with reduced amount of serum. However, in contrast to v-Jun-transformed CEFs, the ATF3 overexpressing cells could not promote colony formation from single cells in agar. Partial transformation induced by ATF3 was found to be associated with repression of multiple cellular genes that are also down-regulated by v-Jun, including those coding for the extracellular components fibronectin, decorin, thrombospondin 2, and the pro-apoptotic protein Par-4. These data demonstrate that, at least in primary avian cells, rat ATF3 possesses an intrinsic oncogenic potential. Moreover, the results suggest that ATF3 might induce growth factor independence by down-regulating a subset of the genes repressed by v-Jun.

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Abbreviations

ATF3:

activating transcription factor 3

AP1:

activating protein 1

CEF(s):

chicken embryo fibroblast(s)

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Acknowledgements

This work was supported by fellowships from the Ministère de la Recherche et de la Technologie (to S Perez) and from the Fondation pour la Recherche Médicale (to S Perez and E Vial). It was also funded by grants from the Association pour la Recherche sur le Cancer, from the Mutuelle Générale de l'Education Nationale, from the European Economic Community Biomedicine and Health Program (Biomed II contract no. BMH4 CT98 3505 to M Castellazzi) and from the Netherlands Organization for Scientific Research (NWO 901-02-221 to H van Dam). We thank the following persons for the gift of various avian cDNA probes: Helene Sage for SPARC, Gilbert Brun for clusterin, Beat Trueb for collagen XII, Sherrill L Adams and Frédéric Mallein-Gérin for α2 (I) collagen, Jack Lawler for thrombospondin 2, Richard Hynes for fibronectin, and Peter K Vogt for HB-EGF. We also thank Pascal Sommer for the gift of the mouse lysyl oxidase cDNA.

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  1. Unité de Virologie Humaine, Institut National de la Santé et de la Recherche Médicale (INSERM-U412), Ecole Normale Supérieure, 46 allée d'Italie, Lyon, 69364, Cedex, 07, France

    Sandrine Perez, Emmanuel Vial & Marc Castellazzi

  2. Department of Molecular Cell Biology, Leiden University Medical Center, Sylvius Laboratories, 2300 RA Leiden, The Netherlands

    Hans van Dam

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Perez, S., Vial, E., van Dam, H. et al. Transcription factor ATF3 partially transforms chick embryo fibroblasts by promoting growth factor-independent proliferation. Oncogene 20, 1135–1141 (2001). https://doi.org/10.1038/sj.onc.1204200

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