SUPPRESSION OF THE NEOPLASTIC PHENOTYPE BY REPLACEMENT OF THE RB GENE IN HUMAN CANCER-CELLS

SUPPRESSION OF THE NEOPLASTIC PHENOTYPE BY REPLACEMENT OF THE RB GENE IN HUMAN CANCER-CELLS
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DOI:
10.1126/science.3201247
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发表时间:
1988-12-16
期刊:
影响因子:
56.9
通讯作者:
LEE, WH
LEE, WH
中科院分区:
综合性期刊1区
文献类型:
--
作者:
HUANG, HJS;YEE, JK;LEE, WH

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视网膜母细胞瘤易感性(RB)基因的突变失活被认为是视网膜母细胞瘤和其他类型人类癌症形成的关键步骤。通过逆转录病毒介导的基因转移,将克隆的RB基因导入到内源性RB基因失活的视网膜母细胞瘤或骨肉瘤细胞中,验证了这一假设。外源性RB基因的表达影响裸鼠细胞形态、生长速度、软琼脂集落形成和致瘤性。单个基因对肿瘤表型的抑制为RB基因在肿瘤发生中的重要作用提供了直接证据。
Mutational inactivation of the retinoblastoma susceptibility (RB) gene has been proposed as a crucial step in the formation of retinoblastoma and other types of human cancer. This hypothesis was tested by introducing, via retroviral-mediated gene transfer, a cloned RB gene into retinoblastoma or osteosarcoma cells that had inactivated endogenous RB genes. Expression of the exogenous RB gene affected cell morphology, growth rate, soft agar colony formation, and tumorigenicity in nude mice. This demonstration of suppression of the neoplastic phenotype by a single gene provides direct evidence for an essential role of the RB gene in tumorigenesis.