PT  - JOURNAL ARTICLE
AU  - Monika Wierdl
AU  - Christopher L. Morton
AU  - Linda C. Harris
AU  - Mary K. Danks
AU  - John D. Schuetz
AU  - Philip M. Potter
TI  - p53-Mediated Regulation of Expression of a Rabbit Liver Carboxylesterase Confers Sensitivity to 7-Ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11)
AID  - 10.1124/jpet.102.044149
DP  - 2003 Feb 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 699--705
VI  - 304
IP  - 2
4099  - http://jpet.aspetjournals.org/content/304/2/699.short
4100  - http://jpet.aspetjournals.org/content/304/2/699.full
SO  - J Pharmacol Exp Ther2003 Feb 01; 304
AB  - We have exploited the ability of wild-type (wt) p53 to repress gene expression and produce tumor-selective cytotoxicity using viral-directed enzyme prodrug therapy. Vectors containing either the cytomegalovirus or Rous sarcoma virus promoter regulating transcription of a rabbit liver carboxylesterase (CE) have been constructed. Upon transfection of these plasmids into cells expressing either wt or mutant p53, differential expression of the CE has been observed, resulting in sensitization of the cells expressing the latter protein to the anticancer prodrug irinotecan, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carb- onyloxycamptothecin (CPT-11). Transduction of isogenic cell lines with adenovirus containing CE under control of the Rous sarcoma virus promoter confirmed the decreased sensitization of cells expressing wtp53 to CPT-11. These studies indicate that the inactivation of wtp53 by mutant p53 in human tumor cells may be sufficient enough to generate a therapeutic window for enhanced cytotoxicity with CPT-11. The American Society for Pharmacology and Experimental Therapeutics