共 85 条
The role of mutant p53 in human cancer
被引:305
作者:

Goh, Amanda M.
论文数: 0 引用数: 0
h-index: 0
机构:
ASTAR, P53 Lab, Singapore 138648, Singapore ASTAR, P53 Lab, Singapore 138648, Singapore

Coffill, Cynthia R.
论文数: 0 引用数: 0
h-index: 0
机构:
Natl Univ Singapore, Inst Mol & Cell Biol, Singapore 117548, Singapore ASTAR, P53 Lab, Singapore 138648, Singapore

Lane, David P.
论文数: 0 引用数: 0
h-index: 0
机构:
ASTAR, P53 Lab, Singapore 138648, Singapore ASTAR, P53 Lab, Singapore 138648, Singapore
机构:
[1] ASTAR, P53 Lab, Singapore 138648, Singapore
[2] Natl Univ Singapore, Inst Mol & Cell Biol, Singapore 117548, Singapore
关键词:
mutant p53;
dominant negative;
gain of function;
p53 family members;
tumour formation and progression;
GAIN-OF-FUNCTION;
TUMOR-SUPPRESSOR FUNCTIONS;
LI-FRAUMENI-SYNDROME;
CELL-CYCLE ARREST;
IN-VIVO;
MOUSE MODEL;
FUNCTIONAL-PROPERTIES;
EMBRYONIC LETHALITY;
MDM2-DEFICIENT MICE;
FUNCTION PHENOTYPE;
D O I:
10.1002/path.2784
中图分类号:
R73 [肿瘤学];
学科分类号:
100214 ;
摘要:
Mutations in the TP53 (p53) gene are present in a large fraction of human tumours, which frequently express mutant p53 proteins at high but heterogeneous levels. The clinical significance of this protein accumulation remains clouded. Mouse models bearing knock-in mutations of p53 have established that the mutant p53 proteins can drive tumour formation, invasion and metastasis through dominant negative inhibition of wild-type p53 as well as through gain of function or 'neomorphic' activities that can inhibit or activate the function of other proteins. These models have also shown that mutation alone does not confer stability, so the variable staining of mutant proteins seen in human cancers reflects tumour-specific activation of p53-stabilizing pathways. Blocking the accumulation and activity of mutant p53 proteins may thus provide novel cancer therapeutic and diagnostic targets, but their induction by chemotherapy may paradoxically limit the effectiveness of these treatments. Copyright. (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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页码:116 / 126
页数:11
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