B12
Human p53 isoforms and cancer
Mustapha Aoubala1, Stephanie Vinot2, Alexandra Diot1, Marie Khoury1, Alastair Thompson1, Anne-Catherine Prats1, David Lane1, Pierre Roux2, Jean-Christophe Bourdon1
1University of Dundee, UK, 2CNRS/University of Montpellier, France
The p53 pathway is ubiquitously lost in cancer cells either by mutation of the p53 gene (50% of the tumours) or by inactivating the interaction of viral or cellular proteins with p53 protein. We recently published the identification of nine p53 isoforms. We established that p53 isoforms bind preferentially to some p53-responsive promoters and can modulate differentially p53 transcriptional activity. We reported also that p53 isoforms are abnormally expressed in breast tumours.
Our analysis of p53 isoform expression in relation with clinical data and outcomes in 171 primary breast tumours suggests that p53 isoforms are involved in carcinogenesis. Our clinical data are supported with experimental evidences demonstrating that p53 isoforms play crucial roles on cell cycle, apoptosis and metastatic process.
In collaboration with Pierre Roux lab who has previously demonstrated that p53 is involved in cell invasion and cell motility (Gadea et al., (2007) J Cell Biol. 2007 Jul 2;178(1):23-30), we established that p53 isoforms differentially modulate cell migration and cell invasion.
Our data may provide an explanation to the difficulties in clinical studies to link p53 status with clinical outcome and cancer treatment.
