John Libbey Eurotext

Bulletin du Cancer

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TP63 gene in stress response and carcinogenesis: a broader role than expected Volume 93, numéro 12, Décembre 2006

Auteurs
International Agency for Research on Cancer, 150 cours Albert-Thomas, 69372 Lyon Cedex 08, France, Inserm Unit 590, Université Lyon 1, 69000 Lyon France, Bât. Cheney A, Centre Léon Bérard, 28 rue Laennec, 69373 Lyon Cedex 08, France

The TP63 gene is a member of the TP53 gene family. In contrast with TP53, this gene is not frequently inactivated by mutation in cancer. Initial experiments with disrupted TP63 have allowed specifying p63 protein a role in the regulation of differentiation and morphogenesis in epithelial and mesenchymal tissues. Nevertheless, there is growing evidence that p63 is also involved in oncogenesis through several mechanisms. Indeed, amplification of TP63 is detected in about 25% of squamous cell carcinomas of lung, head and neck and oesophagus. This results in overexpression of a truncated form of p63 (ΔNp63) that may counteract growth suppression induced by full length p63 (TAp63), as well as by the other family members, p53 and TAp73. Moreover, mice heterozygous for TP63 develop spontaneous tumours. Whereas p53 plays a major role in response to numerous DNA-damaging agents, the involvement of p63 in this process is not well documented. Nevertheless, several groups recently reported that TAp63 can induce cell cycle arrest and apoptosis in DNA-damaged cells, alone or in synergy with chemotherapeutic agents, and thus appears as a chemosensitivity factor. Overall, in addition to non-redundant, specific functions in differentiation and morphogenesis, p63 appears to exert biological functions similar to those of p53 and to take a growing place in oncogenesis and modulation of responses to anti-cancer therapy.