Characterization of the p53 Tumor Suppressor Pathway in Cell Lines of the National Cancer Institute Anticancer Drug Screen and Correlations with the Growth-Inhibitory Potency of 123 Anticancer Agents

摘要: Abstract In the present study, we report characterization of p53 tumor suppressor pathway in 60 cell lines National Cancer Institute (NCI) anticancer drug screen, as well correlations between integrity this and growth-inhibitory potency 123 agents screen. Assessment status these was achieved through complete cDNA sequencing, measurement basal protein levels functional assessment ( a ) transcriptional activity from each line yeast assay, b γ-ray-induced G 1 phase cycle arrest, c expression CIP1/WAF1, GADD45 , MDM2 mRNA. Our investigations revealed that gene mutations were common NCI screen lines: 39 58 analyzed contained mutant sequence. derived almost all failed to transcriptionally activate reporter yeast, majority studied expressed elevated protein. contrast most wild-type -containing lines, cells containing sequence also deficient γ-ray induction mRNA ability arrest following γ-irradiation. Taken together, assessments provided indications These individual subsequently used probe database for “standard agents,” which included clinically approved drugs. have been tested against on multiple occasions, proposed mechanism action had previously assigned agent. analysis with tended exhibit less growth inhibition than when treated agents: including DNA cross-linking agents, antimetabolites, topoisomerase I II inhibitors. Similar uncovered probed using other indices assessed lines. Interestingly, class differed respect antimitotic agents. Growth-inhibitory tended, be independent status. should prove useful researchers investigating fundamental aspects biology pharmacology. This information allows large-scale more 60,000 compounds novel might exploit defective function means preferential toxicity.