Breast cancers lacking estrogen and progesterone receptor expression and Her2 
amplification exhibit distinct gene expression profiles and clinical features, 
and they comprise the majority of BRCA1-associated tumors. Here we demonstrated 
that the p53 family member p63 controls a pathway for p73-dependent cisplatin 
sensitivity specific to these "triple-negative" tumors. In vivo, DeltaNp63 and 
TAp73 isoforms were coexpressed exclusively within a subset of triple-negative 
primary breast cancers that commonly exhibited mutational inactivation of p53. 
The DeltaNp63alpha isoform promoted survival of breast cancer cells by binding 
TAp73 and thereby inhibiting its proapoptotic activity. Consequently, inhibition 
of p63 by RNA interference led to TAp73-dependent induction of proapoptotic 
Bcl-2 family members and apoptosis. Breast cancer cells expressing 
DeltaNp63alpha and TAp73 exhibited cisplatin sensitivity that was uniquely 
dependent on TAp73. Thus, in response to treatment with cisplatin, but not other 
chemotherapeutic agents, TAp73 underwent c-Abl-dependent phosphorylation, which 
promoted dissociation of the DeltaNp63alpha/TAp73 protein complex, 
TAp73-dependent transcription of proapoptotic Bcl-2 family members, and 
apoptosis. These findings define p63 as a survival factor in a subset of breast 
cancers; furthermore, they provide what we believe to be a novel mechanism for 
cisplatin sensitivity in these triple-negative cancers, and they suggest that 
such cancers may share the cisplatin sensitivity of BRCA1-associated tumors.