ANALYSIS OF GLIOMA CELL-LINES FOR AMPLIFICATION AND OVEREXPRESSION OF MDM2

被引:57
作者
HE, J
REIFENBERGER, G
LIU, L
COLLINS, VP
JAMES, CD
机构
[1] EMORY UNIV,SCH MED,DEPT NEUROSURG,MOLEC NEUROONCOL LAB,ATLANTA,GA 30322
[2] KAROLINSKA HOSP,LUDWIG INST CANC RES,S-10401 STOCKHOLM,SWEDEN
[3] KAROLINSKA HOSP,DEPT PATHOL,S-10401 STOCKHOLM,SWEDEN
关键词
D O I
10.1002/gcc.2870110205
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. Genes Chromosom Cancer 11:91-96 (1994). (C) 1994 Wiley-Liss, Inc.
引用
收藏
页码:91 / 96
页数:6
相关论文
共 24 条
  • [11] IDENTIFICATION OF AN AMPLIFIED, HIGHLY EXPRESSED GENE IN A HUMAN GLIOMA
    KINZLER, KW
    BIGNER, SH
    BIGNER, DD
    TRENT, JM
    LAW, ML
    OBRIEN, SJ
    WONG, AJ
    VOGELSTEIN, B
    [J]. SCIENCE, 1987, 236 (4797) : 70 - 73
  • [12] LADANYI M, 1993, CANCER RES, V53, P16
  • [13] LEACH FS, 1993, CANCER RES, V53, P2231
  • [14] MELTZER PS, 1991, CELL GROWTH DIFFER, V2, P495
  • [15] THE MDM-2 ONCOGENE PRODUCT FORMS A COMPLEX WITH THE P53 PROTEIN AND INHIBITS P53-MEDIATED TRANSACTIVATION
    MOMAND, J
    ZAMBETTI, GP
    OLSON, DC
    GEORGE, D
    LEVINE, AJ
    [J]. CELL, 1992, 69 (07) : 1237 - 1245
  • [16] ONCOPROTEIN MDM2 CONCEALS THE ACTIVATION DOMAIN OF TUMOR SUPPRESSOR-P53
    OLINER, JD
    PIETENPOL, JA
    THIAGALINGAM, S
    GVURIS, J
    KINZLER, KW
    VOGELSTEIN, B
    [J]. NATURE, 1993, 362 (6423) : 857 - 860
  • [17] AMPLIFICATION OF A GENE ENCODING A P53-ASSOCIATED PROTEIN IN HUMAN SARCOMAS
    OLINER, JD
    KINZLER, KW
    MELTZER, PS
    GEORGE, DL
    VOGELSTEIN, B
    [J]. NATURE, 1992, 358 (6381) : 80 - 83
  • [18] OLSON DC, 1993, ONCOGENE, V8, P2353
  • [19] REIFENBERGER G, 1993, CANCER RES, V53, P2736
  • [20] REIFENBERGER G, 1991, IMMUNHISTOCHEMIE TUM, P32