CCBIO seminar: Jean-Christophe Bourdon
A decade of research on p53 summarised
Centre for Oncology and Molecular Medicine, Dundee Cancer Centre, and Jacqui Wood Cancer Centre, Ninewells Hospital, University of Dundee, UK
All genetic models, experimental and clinical data indicate that the gene TP53 plays a key role in cancer formation, progression and treatment. For 30 years, it was thought that TP53 is a dedicated tumour-suppressor gene encoding a single transcription factor, p53, which protects cells from genotoxic stress. However, it is poorly understood how a single protein, p53, can be responsive to so many stress signals and orchestrates very diverse cell responses to maintain/restore cell/tissue functions.
It has been uncovered that the TP53 gene physiologically expresses, in a tissue-dependent manner, not one p53 protein but twelve different p53 proteins, with distinct biochemical activities (p53 isoforms). This may prove fundamental when deciphering the p53 pathway and attempting to improve cancer treatment. Over the last decade, all genetic animal models of p53 isoforms (zebrafish, Drosophila and mouse), have consistently indicated that altering expression of a few p53 isoforms, without affecting the expression of the canonical p53 protein (i.e. p53a), promotes different pathologies: premature ageing, (neuro-)degenerative diseases, inflammation, cancer, embryo malformation and altered responses to ionising irradiation or infectious diseases. The p53 isoforms are dynamically reforming in depth the p53 field.
I will summarise a decade of research on p53 isoforms and present our latest experimental and clinical studies in breast cancer that could be extended to predict response to treatment in other types of cancer.
Chairperson: Bjørn Tore Gjertsen, CCBIO