HIGH-LEVELS OF MDM2 ARE NOT CORRELATED WITH THE PRESENCE OF WILD-TYPEP53 IN HUMAN-MALIGNANT MESOTHELIOMA CELL-LINES

Prior analysis of 20 human mesothelioma cell lines for p53 status reve aled only two mutations and one p53 null cell line, although p53 expre ssion was detected in most cell lines. In addition, mRNA and protein e xpression of the retinoblastoma gene product in human mesothelioma cel l lines is similar to normal controls. We have tested for p53 inductio n after exposure to ionising radiation and demonstrate this induction and, to a lesser extent, p21(WAFI) induction, in both normal mesotheli al cells and p53-positive mesothelioma cell lines. We postulated that high levels of MDM2 might alter p53 and retinoblastoma tumour-suppress or function in mesothelioma. However, Southern blot analysis for mdm2 indicated that no amplification had occurred in 18 mesothelioma cell l ines tested. Steady-state mRNA and protein levels also did not indicat e overexpression. These results indicate that high levels of MDM2 are not responsible for inactivating the functions of wild-type p53 or the retinoblastoma gene product during the pathogenesis of malignant meso thelioma.