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Retinoic acid induces TGFβ-dependent autocrine fibroblast growth

Oncogene volume 27, pages 477–489 (2008)Cite this article

Abstract

To evaluate the role of murine TFIID subunit TAF4 in activation of cellular genes by all-trans retinoic acid (T-RA), we have characterized the T-RA response of taf4lox/− and taf4−/− embryonic fibroblasts. T-RA regulates almost 1000 genes in taf4lox/− cells, but less than 300 in taf4−/− cells showing that TAF4 is required for T-RA regulation of most, but not all cellular genes. We further show that T-RA-treated taf4lox/− cells exhibit transforming growth factor (TGF)β-dependent autocrine growth and identify a set of genes regulated by loss of TAF4 and by T-RA corresponding to key mediators of the TGFβ signalling pathway. T-RA rapidly and potently induces expression of connective tissue growth factor (CTGF) via a conserved DR2 type response element in its proximal promoter leading to serum-free autocrine growth. These results highlight the role of TAF4 as a cofactor in the cellular response to T-RA and identify the genetic programme of a novel cross talk between the T-RA and TGFβ pathways that leads to deregulated cell growth.

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Acknowledgements

We thank Dr C Rochette-Egly, Dr F Cammas and Dr Olivier Poch for the antibodies against RARγ and the RARγ and RXRα expression vectors as well as for helpful discussions and bioinformatic analysis, Dr C Hill for the TGFβ responsive 3T3 cells, C Thibault for the affymetrix arrays, and the common services of the IGBMC. This work was supported by grants from the CNRS, INSERM, Ministère de la Recherche et de la Technologie, Association pour la Recherche contre le Cancer and the European Union. ID is an équipe labelisée of the Ligue Nationale et Départementale Région Alsace contre le Cancer.

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  1. Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP. UMR7104, 1 Rue Laurent Fries, Illkirch Cédex, France

    A Fadloun, D Kobi, L Delacroix, D Dembélé, I Michel, A Lardenois, J Tisserand, R Losson, G Mengus & I Davidson

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  1. A Fadloun
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  2. D Kobi
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  3. L Delacroix
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Correspondence to I Davidson.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Fadloun, A., Kobi, D., Delacroix, L. et al. Retinoic acid induces TGFβ-dependent autocrine fibroblast growth. Oncogene 27, 477–489 (2008). https://doi.org/10.1038/sj.onc.1210657

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