Loss of PML cooperates with mutant p53 to drive more aggressive cancers in a gender-dependent manner
Sue Haupt, Catherine Mitchell, Vincent Corneille, Jake Shortt, Stephen Fox, Pier Paolo Pandolfi, Mireia Castillo-Martin, Dennis M Bonal, Carlos Cordon-Cardo, Guillermina Lozano, Ygal Haupt
CELL CYCLE | TAYLOR & FRANCIS INC | Published : 2013
UNLABELLED: p53 mutations and downregulation of promyelocytic leukemia (PML) are common genetic alterations in human cancers. In healthy cells these two key tumor suppressors exist in a positive regulatory loop, promoting cell death and cellular senescence. However, the influence of their interplay on tumorigenesis has not been explored directly in vivo. The contribution of PML to mutant p53 driven cancer was evaluated in a mouse model harboring a p53 mutation (p53 (wild-type/R172H) ) that recapitulates a frequent p53 mutation (p53 (R175H) ) in human sporadic and Li-Fraumeni cancers. These mice with PML displayed perturbation of the hematopoietic compartment, manifested either as lymphoma or..View full abstract
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Awarded by National Health and Medical Research Council (NHMRC) of Australia
The work was supported by grants from the National Health and Medical Research Council (NHMRC) of Australia to Y.H. (NHMRC 509197); by the VESKI award and CASS Foundation. Y.H. is an NHMRC Senior Research Fellow.