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 Printable version |
Implication of alternative splice transcripts of caspase-3 and survivin in chemoresistance |
Bulletin du Cancer. Volume 92, Number 3, 219-26, Mars 2005, Synthèse
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 Résumé
Article gratuit
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Author(s) : Frédérique Vegran, Romain Boidot, Claire Oudin, Jean-Marc Riedinger, Sarah Lizard-Nacol |
Summary : Recent studies have shown that resistance to apoptosis may contribute to chemoresistance. Alteration of caspases, such as caspase-3, results on decreased apoptosis. Genes of IAP (inhibitor of apoptosis proteins) family, such as survivin, were also implicated in tumor development where they are mutated or have deregulated expression. Initial studies revealed strong survivin expression in several fetal tissues and some proliferating adult tissues, whereas no survivin expression was detected in a range of adult tissues. Although the factors at the origins on survivin re-expression in tumors are still unknown, the anti-apoptotic function of survivin is mediated in part by inhibiting caspase-3 activity. Recently, functionally divergent splice variants resulting from alternative splicing, with apoptotic (for caspase-3) or anti-apoptotic (for survivin) opposite activities have been described. The alternative splice variant, caspase-3s results from exon 6 deletion and shows antagonist of apoptotic property of caspase-3. Three alternative splice variants of survivin (survivin-ΔEx3, survivin-2B and survivin-3B) differing in their anti-apoptotic properties were reported. While the anti-apoptotic effect of survivin-ΔEx3 is preserved, survivin-2B has lost its anti-apoptotic potential and may act as a naturally occurring antagonist of survivin and survivin-ΔEx3. At present, little is known about properties of survivin-3B. Several evidences indicate that in several cancers, the ratio of splice variants is significantly altered, and modifications of splicing pathways have been developed for cancer treatment. Recent investigations have shown that expression of alternative splice variants of caspase-3 and of survivin were also altered in many human cancers, and that variations in their expression were associated with tumor progression and chemoresistance. In this article, we describe recent data concerning alternative splice variants of these two proteins. |
Keywords : apoptosis, caspase-3, survivin, splice variant transcript, tumor progression, chemoresistance |
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