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Transcriptional control of SPARC by v-Jun and other members of the AP1 family of transcription factors

Oncogene volume 19, pages 5020–5029 (2000)Cite this article

Abstract

Transformation of chick embryo fibroblasts by the v-Jun oncoprotein correlates with a down-regulation of the extracellular matrix protein SPARC and repression of the corresponding mRNA. Alteration in SPARC expression has been repeatedly reported in human cancers of various origin, and is thought to contribute to the remodeling of the extracellular matrix during neoplastic progression. Transcriptional control of SPARC is poorly understood. We show here that (i) v-Jun-mediated repression of the endogenous SPARC gene is enhanced by Fra2 but alleviated by ATF2, Fra2 and ATF2 being the two major partners of v-Jun in the transformed cells; (ii) high basal activity as well as repression by v-Jun and modulation by Fra2 and ATF2 is restricted to a small proximal fragment (−124/+16) of the chicken SPARC promoter; (iii) the activity of this minimal promoter is modulated by all the AP1 family members known in chickens (c-Jun and JunD; c-Fos and Fra2; ATF2; c-Maf, MafA, and MafB). Taken together these data demonstrate that, at least in avian primary cells, SPARC expression is under the control of the AP1 transcription factor. Further studies with the minimal (−124/+16) promoter fragment are needed to understand how this control takes place at the molecular level.

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Abbreviations

CEF(s):

chicken embryo fibroblast(s)

REF(s):

rat embryo fibroblast(s)

SPARC:

secreted protein, acidic, and rich in cysteine

AP1:

activating protein 1

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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 E Vial). This work was also funded by grants from the Association pour la Recherche sur le Cancer, from the Mutuelle Générale de l’Education Nationale, as well as from the European Economic Community Biomedicine and Health Program (Biomed II contract N° BMH4 CT98 3505 to M Castellazzi). We are grateful to the following people for the gift of various DNA probes: Marie-Paule Felder-Schmittbuhl for the coding sequence of MafA, Makoto Nishizawa for the coding sequence of MafB and c-Maf, and Martin Hafner for the gift of the −1409/+28 human SPARC promoter. We thank Joël Baguet for the construction of the GST-Fra2 and GST-c-Maf plasmids and for the recovery of the fusion proteins. We also thank Robin Buckland and Karen Perrigo for a critical reading of the manuscript.

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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, 69364 Cedex 07, Lyon, France

    Emmanuel Vial, Sandrine Perez & Marc Castellazzi

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Vial, E., Perez, S. & Castellazzi, M. Transcriptional control of SPARC by v-Jun and other members of the AP1 family of transcription factors. Oncogene 19, 5020–5029 (2000). https://doi.org/10.1038/sj.onc.1203867

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