B13

p53β and p53γ isoform expression may abrogate poor prognosis in patients with p53 mutant breast cancer

Jean-Christophe Bourdon, Alexandra Diot, Mustapha Aoubala, Marion Lahmani, Lee Baker, Phil Quinlan, Colin Purdie, Lee Jordan, Alastair Thompson

University of Dundee, UK

p53 is a key gene in cancer and response to anticancer therapies. p53 mutation is associated with therapeutic resistance and poor survival in breast cancer. In 129 primary breast cancers (22.5% mutant), 63.6% of breast cancers demonstrated loss of p53β and 62.8% loss of p53γ splice variants.

p53 mutation was significantly associated with poor survival. However, patients with cancers expressing p53β or p53γ isoforms in the presence of p53 mutation had comparable survival curves to those without p53 mutation. We confirmed by luciferase assay that p53β and p53γ enhances p53 transcriptional activity on bax promoter in response to doxorubicin treatment. Moreover, WTp53γ and mutant p53γ can induce apoptosis in response to doxorubicin treatment. Interestingly, mutant p53γ is not inactivated by mutation that inhibit p53.

p53β and p53γ may contribute to the contradictory literature on p53 in breast cancer and suggests that the interpretation of p53 mutation testing in clinical trials and therapeutic decision making merits further evaluation.