Adenovirus-mediated p53 gene transfer to human breast tumour cells in vitro

Functional inactivation of the p53 gene is associated with increased resistance to radiation and genotoxic drugs and poor prognosis in breast cancer. Reconstitution of the p53-dependent apoptotic pathway by gene transfer of a recombinant wild-type p53 minigene results in rapid apoptotic cell death in breast and other cancer cell types expressing null or mutant p53. This strategy has therefore become a major focus of efforts aimed at the development of gene therapy protocols for the treatment of breast and other cancers. This thesis examines the potential of adenoviral vectors for gene transfer to human breast cancer cells in terms of infection efficiencies, transgene expression, and recombinant wild-type p53-mediated apoptosis in vitro. It was found that adenoviral vector is efficient for transferring human wild-type p53 gene to human breast tumour cells and that overexpression of wild-type p53 led to apoptotic cell death in cells transduced, regardless of their endogenous p53 status. However, cells expressing mutant p53 were more sensitive to this cell death induction than cells expressing wild-type p53.