MP36-16 THE ROLE OF P63 AND P53MUTANT IN THE REGULATION OF DNA REPAIR, MUTATOR AND INVASIVE PHENOTYPE OF BLADDER CANCER CELLS

Abstract

It is well established that the two major phenotypic variants of human bladder cancers, the low-grade non-invasive papillary bladder carcinoma (N-Inv-BC) and the high-grade invasive BC (Inv-BC), have different molecular features. For example, compared to 10% in N-Inv-BC, p53 point mutations are found in 70% of Inv-BC. p63 expression is suppressed in aggressive BC. In contrast, more than 70% of N-Inv-BC have FGFR3 mutations compared to the 10% found in Inv-BC. Using well-established human BC cell lines, we found that while Inv-BC cells have a mutator phenotype, N-Inv-BC cells do not. N-Inv-BC cells are proficient in nucleotide excision repair and base excision repair, whereas Inv-BC are deficient in both, and the expression of several DNA repair genes is suppressed in Inv-BC cells. This study aims to understand the role of p63, mutated p53, DNA repair function and cell mutation susceptibility to BC development. Background