F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología
Doi
Abstract
p63 and p73, the two other members of the
p53 family, were identified almost 15 years ago. Here,
we review their potential use for diagnosis, prognosis
and prediction of response to therapy in various cancers.
The two genes show distinct expression patterns in both
normal and cancer tissues and each gene gives rise to
multiple protein isoforms with different activities,
including those with tumour-suppressor or oncogenic
effects. Despite such complexity, some common themes
emerge; p63 is commonly overexpressed as the ΔNp63
isoform and sometimes associated with TP63
amplification, whereas p73 is often reduced (by
methylation or gene loss), or there is an increase in the
ratio of ΔNp73 to TAp73. These generalisations do not
apply universally; TAp63 is overexpressed in
haematological malignancies, TP63 mis-sense mutations
have been reported in squamous cancers and TP63
translocations occur in lymphomas and some lung
adenocarcinomas. There are associations with disease
prognosis and response to specific therapies in
individual cancer types for both p63 and p73, making
their analysis of clinical relevance. We also discuss their
utility for aiding in differential diagnosis, which has
been demonstrated for p63, but not yet for p73.
Throughout, we highlight the discrepant nature of many
studies due to the variable methodologies employed, the
lack of systematic evaluation of isoforms and the
problems of poor antibody characterization and crossreactions within the p63/p73 family. Finally, we
emphasize the value of recently developed isoformspecific reagents that have clear advantages for the study
of p63 and p73 experimentally and clinically