| Abstrakt: |
One of the mechanisms in which anticancer therapies function is to induce cell death by apoptosis. In this regard, the biological activity of p53 may be critical since the presence of p53 appears to play a role in apoptosis following genotoxic stress. In experimental systems using in vitro transformed primary cells, there is a direct correlation between the presence of p53 and apoptosis. For example, E1A/ras-transformed primary mouse fibroblasts are less viable and undergo apoptosis following genotoxic stress if these cells contain a wild type p53. In comparison, similarly transformed cells which are p53-deficient are more viable and will not undergo apoptosis under these conditions. Although these are important observations, it remains to be established whether there exists a similar relationship between the presence of wild type p53 and loss of cell viability following therapy in human tumour cells. One way to address this question is to target wild type p53 in human tumour cells using human papillomavirus E6 which mediates the degradation of wild type p53 through the ubiquitin pathway. In this manner, E6 engineered p53-deficient and parental p53-containing human tumour cells provides an appropriate experimental system in which to determine whether wild type p53 in tumour cells has influence on cell viability following genotoxic anticancer treatments. In the present study, the wild type p53 protein in human fibrosarcoma HT1080 cells were targeted with HPV-18 E6 and the viability of these cells in response to treatment with adriamycin, u.v.-irradiation and gamma-irradiation was examined. Data is presented which shows that p53-containing and p53-deficient cells were equally sensitive to these treatments. These data argue that the wild type p53 in these tumour cells does not cause these cells to be less viable when treated with anticancer agents or u.v.-irradiation. Therefore, the status of p53 alone in tumour cells may not be an indicator of response to anticancer treatments. |
