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The role of mutant p53 in human cancer
Author(s) -
Goh Amanda M,
Coffill Cynthia R,
Lane David P
Publication year - 2011
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2784
Subject(s) - mutant , biology , mutation , mutant protein , cancer research , cancer , metastasis , p53 protein , cancer cell , microbiology and biotechnology , gene , genetics
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 © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.