FREQUENT INACTIVATION OF THE RETINOBLASTOMA ANTIONCOGENE IS RESTRICTED TO A SUBSET OF HUMAN TUMOR-CELLS

FREQUENT INACTIVATION OF THE RETINOBLASTOMA ANTIONCOGENE IS RESTRICTED TO A SUBSET OF HUMAN TUMOR-CELLS
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DOI:
10.1073/pnas.87.7.2775
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发表时间:
1990-04-01
影响因子:
11.1
通讯作者:
WEINBERG, RA
WEINBERG, RA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
HOROWITZ, JM;PARK, SH;WEINBERG, RA

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我们使用多克隆抗合成肽血清研究视网膜母细胞瘤基因(RB)失活在多种人类肿瘤细胞系中的作用。我们的分析表明,RB蛋白,p105-Rb的失活,是普遍的视网膜母细胞瘤细胞,证明预测的Knudson“两击”假说。此外,我们的分析表明,RB基因的失活在更常见的人类肿瘤小细胞肺癌中几乎同样频繁。三分之一的膀胱癌也携带改变或缺乏p105-Rb。相比之下,其他人类肿瘤仅表现出RB基因的罕见失活。这些结果表明RB基因的失活是人类肿瘤发病机制中的一个关键步骤。
We have used polyclonal anti-synthetic peptide serum to study the role of retinoblastoma gene (RB) inactivation in a variety of human tumor cell lines. Our analysis indicates that inactivation of the RB protein, p105-Rb, is universal in retinoblastoma cells, vindicating the predictions of the Knudson "two-hit" hypothesis. In addition, our analysis has shown that inactivations of the RB gene are nearly as frequent in a more common human tumor, small cell lung carcinoma. One-third of bladder carcinomas surveyed also carry altered or absent p105-Rb. Other human tumors by contrast demonstrate only infrequent inactivation of the RB gene. These reuslts suggest that inactivation of the RB gene is a critical step in the pathogenesis of a subset of human tumors.