[Clearing up the p16INK4a-p14/p19ARF imbroglio?].
Since its discovery, the CDKN2/MTS1 locus has been considered as an important site for the understanding of cell cycle deregulations that are involved in cancer cell generation. A comprehensive approach of the respective roles played by the two p16INK4a and p14/p19ARF (ARF) proteins encoded by this locus was not yet achieved because of the structural intrication of their genes. Inactivation of the only p16INK4a gene in mouse allowed to get better insight into this puzzle. In vivo results presented by de Pinho's group showed that inactivation of both p16INK4a alleles generated a panel of various types of tumors from the 28th week following birth. Bern's group dit not confirm this result but showed that the presence of only one ARF functional copy increases sensitivity of p16-/- mice to tumor occurrence indicating that insufficient dosage of ARF protein may facilitate tumorigenesis. It seems now established that, at least in mouse, ARF controls senescence in vitro, immortalisation and transformation by oncogenic ras. p16INK4a inactivation appears to be crucial for the induction of carcinogens-induced tumors.
Larsen
C J
CJ
Laboratoire d'oncologie moléculaire, IBMIG, 40, avenue du Recteur-Pineau, 86022, Poitiers. c.j.larsen@chu-poitiers.fr
D000818:Animals; D002273:Carcinogens; D002455:Cell Division / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts / Q000502:physiology; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000139:chemically induced / Q000235:genetics*; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics / Q000502:physiology*
D002273:Carcinogens; C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D025803:Tumor Suppressor Protein p14ARF