Cells having oncogene-suppressed p53-mediated apoptosis and methods of use to identify anti-oncogenic compounds

摘要

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.