Abstracts
Résumé
Nous avons identifié un nouveau gène, appelé p8, dont l’expression est fortement induite dans le pancréas durant la phase aiguë de la pancréatite. Le gène p8 code pour une protéine nucléaire de 82acides aminés. L’expression de l’ARNm de p8 s’observe dans d’autres tissus que le pancréas. Elle est activée par de nombreux agents de stress et ne nécessite pas une forte agression pour apparaître. L’analyse biochimique et biophysique de la protéine recombinante a révélé de grandes analogies structurales avec les protéines HMG (high mobility group), bien que leur séquence primaire ne présente que de faibles similitudes. Nous avons observé que p8 était surexprimée dans de nombreux cancers humains. La voie de réponse au stress cellulaire contrôlée par p8 pourrait donc être impliquée dans la formation de ces tumeurs. Chez la souris nude, l’injection sous-cutanée ou intrapéritonéale de fibroblastes transformés conduit à la formation de tumeurs, alors qu’aucune formation tumorale n’est observée quand les fibroblastes utilisés proviennent de souris p8–/–, dans lesquelles le gène p8 a été spécifiquement inactivé. L’expression de p8, au travers des mécanismes de réponse au stress qu’elle permet, est donc nécessaire au développement de ces tumeurs.
Abstract
We identified a new gene, called p8, which showed a strong induction during the acute phase of pancreatitis. Further experiments have shown that p8 mRNA is activated in response to several stresses and that its activation is not restricted to pancreatic cells. p8 is a nuclear protein and biochemical and biophysical studies showed that p8 was in many structural aspects very similar to the HMG (high mobility group) proteins, although sharing with them low amino acid sequence homology. Also, p8 was found overexpressed in many human cancers. Therefore, we wondered whether the p8-mediated response to cellular stress was necessary for tumor establishment. Subcutaneous or intraperitoneal injections of transformed p8-expressing fibroblasts led to tumor formation in nude mice, but no tumor was observed with transformed p8-deficient cells. Restoring p8 expression in transformed p8-deficient fibroblasts led to tumor formation demonstrating that p8 expression is necessary for tumor development and suggesting that the stress-response mechanisms governed by p8 are required for tumor establishment.
Appendices
Références
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