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The specific activation of gadd45 following UVB radiation requires the POU family gene product N-oct3 in human melanoma cells

Oncogene volume 20, pages 7375–7385 (2001)Cite this article

Abstract

Here we report the specific regulation of gadd45 expression in human melanoma cell lines following UVB radiation. This solar wavelength is likely to be involved in melanoma aetiology. We have previously shown that gadd45 expression is strongly enhanced in a p53-independent manner following UVB irradiation, unlike the other p53 target genes studied. Furthermore, gadd45 is specifically activated in melanocytes since its induction in response to UVB, is not observed in other skin cells such as keratinocytes or fibroblasts. To investigate this particular regulation of gadd45, we analysed the UVB-induced response of different gadd45 promoter regions. Thus, a minimal promoter region of 50 bp length, responsible for gadd45 activation in melanoma cell lines following UVB irradiation, was determined. In electrophoretic mobility shift assays (EMSAs), we showed that this region (−106/−56) of the gadd45 promoter which contains two identical octamers, binds the POU family gene products oct-1 and N-oct3. Given the specific expression pattern of N-oct3 in melanocyte, we invalidated the expression of this transcription factor in melanoma cells: such an abrogation of N-oct3 protein expression in melanoma cells impeded gadd45 UVB-response. Thus the response of melanocyte to UVB may use an original and previously undescribed pathway.

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Acknowledgements

We thank J Franchi for providing the human normal primary keratinocytes (Parfums Christian Dior, France) and M Strubin, U Malipiero and W Schaffner (Zürich) for the gift of various plasmids. We thank Marie-Dominique Reynaud for editorial assistance and R Pedeux, M Kallassy, M Billaud and ML Vignais for helpful discussions. This work was supported by INSERM and by grants from the ‘Association pour la Recherche sur le Cancer’ (ARC 5649) and from the ‘Ligue contre le Cancer - Comité Départemental du Rhône’. K Lefort is a recipient of a fellowship from the ‘Ligue contre le Cancer - Comité Départemental de la Haute-Savoie’.

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  1. INSERM U453, Centre Léon Bérard, 28 rue Laënnec, LYON, cedex 08, 69373, France

    Karine Lefort, Jean-Pierre Rouault, Lise Tondereau, Jean-Pierre Magaud & Jean-François Doré

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  1. Karine Lefort
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Correspondence to Jean-François Doré.

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Lefort, K., Rouault, JP., Tondereau, L. et al. The specific activation of gadd45 following UVB radiation requires the POU family gene product N-oct3 in human melanoma cells. Oncogene 20, 7375–7385 (2001). https://doi.org/10.1038/sj.onc.1204923

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