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    • 1. 发明授权
    • Cells having oncogene-suppressed p53-mediated apoptosis and methods of
use to identify anti-oncogenic compounds
    • 具有致癌基因抑制p53介导的凋亡的细胞和用于鉴定抗致癌化合物的方法
    • US5604113A
    • 1997-02-18
    • US224209
    • 1994-04-07
    • Eileen WhiteShuin-Kwei ChiouHuey-Jen L. Lin
    • Eileen WhiteShuin-Kwei ChiouHuey-Jen L. Lin
    • G01N33/50C12Q1/02C12N5/06
    • G01N33/5011
    • The present invention is a method for determining if a compound potentially modulates the ability of a putative oncogene to suppress p53-mediated effects, comprising (A) adding an amount of said compound to genetically engineered cells that express (i) a gene product that induces p53 mediated apoptosis; (ii) a gene product for a p53 gene, wherein either the gene or the gene product are externally controllable; and (iii) a putative oncogene that inhibits the effect of the gene product that induces p53 mediated apoptosis, and (B) examining said cells to determine whether apoptosis has occurred. In particular, the invention provides a method wherein said gene product that induces p53 mediated apoptosis is adenovirus gene E1A, wherein said externally controllable p53 gene product is a temperature-sensitive mutant of p53, and wherein the putative oncogene is selected from the group bcl-2, ras, or the adenovirus E1B(19K) gene. In addition, the invention provides genetically engineered cell lines that can be used to carry out the methods described.
    • 本发明是一种用于确定化合物是否潜在地调节推定的癌基因抑制p53介导的作用的能力的方法,其包括(A)向转基因工程细胞中加入一定量的所述化合物,所述细胞表达(i)诱导的基因产物 p53介导凋亡; (ii)p53基因的基因产物,其中所述基因或基因产物可外部控制; 和(iii)抑制诱导p53介导的凋亡的基因产物的作用的推定的癌基因,和(B)检查所述细胞以确定是否发生细胞凋亡。 特别地,本发明提供了一种方法,其中所述诱导p53介导的细胞凋亡的基因产物是腺病毒基因E1A,其中所述外部可控的p53基因产物是p53的温度敏感突变体,其中推定的致癌基因选自bcl- 2,ras或腺病毒E1B(19K)基因。 此外,本发明提供可用于实施所述方法的基因工程细胞系。