P53 AND BREAST CANCER, AN UPDATE.
Marc Lacroix, Robert-Alain Toillon, Guy Leclercq
Endocrine-Related Cancer (2006) 13, 293-325
P53 plays a key role in mediating cell response to various stresses,
mainly by inducing or repressing a number of genes involved in cell cycle arrest, senescence, apoptosis,
DNA repair, angiogenesis. According to this important function, P53 activity is controlled in a very
complex manner, including several auto-regulatory loops, through the intervention of dozens of modulator
proteins (the “P53 interactome”). P53 mutations are observed in a significant minority of breast tumours.
In the remaining cases, alterations of interactome components or target genes could contribute, to some
extent, to reduce the ability of P53 to efficiently manage stress events. While the prognostic and
predictive value of P53 is still debated, there is an increasing interest for P53-based therapies. The
present paper aims to provide updated information on P53 regulation and function, with specific interest
on its role in breast cancer.
Summary
Genomic and non-genomic actions of P53
Biochemical modifications of P53
Ubiquitin-independent P53 degradation
Modulation of P53 activity
The key role of MDM2
Growth factors, MDM2 and P53
MDM4 (MDMX), MDM2 and P53
Interactions between P53 and P63/P73
Mechanisms of P53 apoptosis vs. growth arrest – P53 apoptotic co-regulators
Others interactors modulating the P53 transcriptional activity
Auto-regulatory loops in P53 action
Mechanisms for loss of P53 activity in cancer
Alterations of P53 modulator and/or target proteins
Hereditary breast cancer and P53
P53 alterations, breast tumour characteristics, and prognosis
P53 alterations and response to therapy
Additional comments on P53 and therapy
P53 as a survival factor during therapy
P53-independent apoptosis
P53 pathway-based therapies
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Affiliations:
Laboratoire Jean-Claude Heuson de Cancérologie Mammaire, Institut Jules Bordet - Université Libre de Bruxelles (ULB), Bruxelles
(Brussels), Belgique (Belgium) (M.L., R.-A.T., G.L.)
InTextoResearch, 4 chemin de Hoevel, 4837 Baelen, Belgique (Belgium) (M.L.)
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