DIFFERENTIAL P53, P21, MDM2 AND RB REGULATION IN GLIOMA CELL-LINES THAT OVEREXPRESS WILD-TYPE P53

Gliomas are part of a subset of tumors in which overexpression of p53 protein in the absence of p53 gene mutation has been described. We hav e utilized a series of glioma cell lines to study the effects of ioniz ing radiation on the regulation of p53, p21, mdm2 and Rb proteins. The induction of p53 protein in glioma cell lines that overexpress wild-t ype p53 differs from normal control cells and glioma cell lines contai ning mutant p53. Alterations in the accumulation of p53 and p21 protei ns are associated with diminished Rb hypophosphorylation. Gliomas that overexpress wild-type p53 also express high levels of mdm2 protein an d exhibit a radiosensitivity that is intermediate between normal cells and cells with mutant p53. These findings suggest that, at least in c ertain glioma cell lines that over-express p53 which is wild-type in s equence, the function of p53 protein is abnormal.