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 have utilized a series of glioma cell lines to study the effects of ionizing radiation on the regulation of p53, p21, mdm2 and Rb proteins. The induction of p53 protein in glioma cell lines that overexpress wild-type p53 differs from normal control cells and glioma cell lines containing mutant p53. Alterations in the accumulation of p53 and p21 proteins are associated with diminished Rb hypophosphorylation. Gliomas that overexpress wild-type p53 also express high levels of mdm2 protein and exhibit a radiosensitivity that is intermediate between normal cells and cells with mutant p53. These findings suggest that, at least in certain glioma cell lines that over-express p53 which is wild-type in sequence, the function of p53 protein is abnormal.
Department of Cancer Biology, School of Public Health, Harvard University, Boston, MA 02115, USA.
M J
MJ
Pykett
E
E
Azzam
W
W
Dahlberg
J B
JB
Little
D001253:Astrocytes / Q000378:metabolism / Q000528:radiation effects; D015153:Blotting, Western; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins; D015689:Oncogene Protein p21(ras) / Q000096:biosynthesis* / Q000378:metabolism; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D016160:Retinoblastoma Protein / Q000096:biosynthesis* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D015689:Oncogene Protein p21(ras)