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EMBO reports 3, 2, 165–170 (2002)
doi:10.1093/embo-reports/kvf023 Published online: February 2002
p8 is critical for tumour development induced by rasV12 mutated protein and E1A oncogene
Sophie Vasseur1, Albrecht Hoffmeister1, Stéphane Garcia1, 2, Claude Bagnis3, Jean-Charles Dagorn1 & Juan Lucio Iovanna1
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1 Centre de Recherche INSERM, EMI 0116, 163 avenue de Luminy, Campus de Luminy, BP 172, F-13009 Marseille, France
2 Hôpital Nord, Chemin des Bourrellys, F-13915 Marseille, France
3 Institut Paoli-Calmettes, Centre de Thérapie Génique de Marseille, 27 boulevard Lei Roure, F-13009 Marseille, France
To whom correspondence should be addressed
Juan Lucio Iovanna Tel: +33 4 91 827533; Fax: +33 4 91 826083; iovanna@marseille.inserm.fr
Received 15 June 2001; Accepted 23 November 2001.
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Abstract
The p8 protein is involved in the cellular stress response of many tissues. Because p8 is overexpressed in many cancers, we investigated whether its expression was required for tumour development. Mouse embryo fibroblasts (MEFs) from p8+/+ and p8-/- animals were transformed with the pBabe-rasV12/E1A retroviral vector, which expresses both the rasV12 mutated protein and the E1A oncogene. As expected, transformed p8+/+ MEFs could form colonies in soft agar. However, transformed p8-/- MEFs could not. In addition, subcutaneous or intraperitoneal injections of transformed p8+/+ MEFs always led to tumour formation in nude mice, but, again, no tumour was observed with transformed p8-/- MEFs. However, restoring p8 expression in transformed p8-/- MEFs before injection led to tumour formation. In the tumours, p8 expression was induced during tumour development. It was concluded that p8 expression in transformed MEFs is necessary for tumour formation, suggesting that the stress-response mechanisms governed by p8 are required for tumour establishment.
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