TY - JOUR
T1 - Analysis of glioma cell lines for amplification and overexpression of MDM2
AU - He, Ju
AU - Reifenberger, Guide
AU - Liu, Lu
AU - Collins, V. Peter
AU - James, C. David
PY - 1994/10
Y1 - 1994/10
N2 - Recently, amplification of the gene encoding a p53 binding protein, MDM2, was determined in 8% of the cases constituting a large series of glioblastomas. Here we have utilized Southern blot analysis to examine 30 cell lines established from such tumors, and our investigation has revealed large increases in MDM2 gene dosage in two cases, one of which showed coamplification of the CDK4 gene that resides in close proximity to MDM2 in chromosomal region 12q13–14. Northern analysis demonstrated overexpression of MDM2 mRNA in the two cell lines with gene amplification, and overexpression of MDM2 protein was evident in each of these by immunohistochemical and Western blot analysis. Analysis of TP53 cDNAs revealed normal TP53 sequences in the cell lines with MDM2 amplification; these results are consistent with those of previous studies suggesting that MDM2 amplification occurs only in tumors expressing wild‐type p53. In total, these data suggest that MDM2 amplification in glioblastoma cell lines occurs at a frequency (6.7%) comparable to that determined in primary tumors; occurs in cell lines expressing wild‐type p53; and can involve the coamplification of additional genes.
AB - Recently, amplification of the gene encoding a p53 binding protein, MDM2, was determined in 8% of the cases constituting a large series of glioblastomas. Here we have utilized Southern blot analysis to examine 30 cell lines established from such tumors, and our investigation has revealed large increases in MDM2 gene dosage in two cases, one of which showed coamplification of the CDK4 gene that resides in close proximity to MDM2 in chromosomal region 12q13–14. Northern analysis demonstrated overexpression of MDM2 mRNA in the two cell lines with gene amplification, and overexpression of MDM2 protein was evident in each of these by immunohistochemical and Western blot analysis. Analysis of TP53 cDNAs revealed normal TP53 sequences in the cell lines with MDM2 amplification; these results are consistent with those of previous studies suggesting that MDM2 amplification occurs only in tumors expressing wild‐type p53. In total, these data suggest that MDM2 amplification in glioblastoma cell lines occurs at a frequency (6.7%) comparable to that determined in primary tumors; occurs in cell lines expressing wild‐type p53; and can involve the coamplification of additional genes.
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U2 - 10.1002/gcc.2870110205
DO - 10.1002/gcc.2870110205
M3 - Article
C2 - 7529554
AN - SCOPUS:0027969332
SN - 1045-2257
VL - 11
SP - 91
EP - 96
JO - Genes, Chromosomes and Cancer
JF - Genes, Chromosomes and Cancer
IS - 2
ER -