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The rebel angel: Mutant p53 as the driving oncogene in breast cancer.

Walerych D
•
Napoli M
•
COLLAVIN, LICIO
•
DEL SAL, GIANNINO
2012
  • journal article

Periodico
CARCINOGENESIS
Abstract
Breast cancer is the most frequent invasive tumor diagnosed in women, causing over 400 thousand deaths yearly worldwide. Like other tumors, it is a disease of a complex, heterogeneous genetic and biochemical background. No single genomic or metabolic condition can be regarded as decisive for its formation and progression. However, a few key players can be pointed out and among them the TP53 tumor suppressor gene, being commonly mutated in breast cancer. In particular, TP53 mutations are exceptionally frequent and apparently among the key driving factors in the triple negative breast cancer (TNBC) - the most aggressive breast cancer subgroup whose management still represents a clinical challenge. The majority of TP53 mutations result in the substitution of single aminoacids in the central region of the p53 protein, generating a spectrum of variants ("mutant p53" for short). These mutants lose to various extent the normal p53 oncosuppressive functions, but can also acquire oncogenic properties by gain-of-function (GOF) mechanisms.This review discusses the molecular processes translating gene mutations to the pathologic consequences of mutant p53 tumorigenic activity, reconciling cell and animal models with clinical outcomes in breast cancer. Existing and speculative therapeutic methods targeting mutant p53 are also discussed, taking into account the overlap of mutant and wild-type (wt) p53 regulatory mechanisms and the crosstalk between mutant p53 and other oncogenic pathways in breast cancer. The studies described here concern breast cancer models and patients - unless it is indicated otherwise and justified by the importance of data obtained in other models.
DOI
10.1093/carcin/bgs232
WOS
WOS:000310624400001
Archivio
http://hdl.handle.net/11368/2591020
info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84868613148
Diritti
metadata only access
Soggetti
  • mutant p53

  • triple negative breas...

  • Pharmacological thera...

Web of Science© citazioni
216
Data di acquisizione
Mar 27, 2024
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