The great MYC escape in tumorigenesis.
Increased wild-type MYC expression occurs frequently in human cancers, except in Burkitt's lymphoma, where the translocated MYC allele is frequently mutated at several hotspots, including a major one at threonine-58. Acute MYC expression increases p53 or ARF levels and induces apoptosis, and previous transgenic animal studies revealed frequent inactivating mutations of p53 or p19ARF in transgenic Myc-induced lymphomas. Lowe and coworkers (Hemann et al., 2005) demonstrate that wild-type MYC can also trigger apoptosis by inducing Bim, which neutralizes Bcl-2. In contrast, the MYC point mutants failed to induce Bim, promoting murine lymphomas that escaped both wild-type p53 and p19ARF, and in doing so, evaded apoptosis.
Dang
Chi V
CV
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. cvdang@jhmi.edu
O'donnell
Kathryn A
KA
Juopperi
Tarja
T
D000818:Animals; D017209:Apoptosis; D002051:Burkitt Lymphoma / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D008223:Lymphoma / Q000235:genetics / Q000473:pathology; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology