Differential expression of DNA topoisomerase I gene between CPT-11 acquired- and native-resistant human pancreatic tumor cell lines: detected by RNA/PCR-based quantitation assay

Biochem Biophys Res Commun. 1992 Apr 30;184(2):618-25. doi: 10.1016/0006-291x(92)90634-w.

Abstract

RNA/PCR quantitation method was developed to determine DNA Topoisomerase I(Topo I)-specific mRNA in order to study its gene expression in CPT-11 sensitive, acquired- or native-resistant human pancreatic tumor cell lines. The results were supported by Northern blotting and Western blotting analyses. Acquired-resistant cells have shown decreased levels of Topo I mRNA, compared with their parental cells. On the contrary, in the wild type cells no correlation was shown between sensitivity and gene expression. On the other, specific Topo I activity of the native resistant cell lines was fairly lower than that of sensitive cell lines, suggesting that immunoreactive Topo I protein contains low levels of active form enzyme which could be targets of CPT-11 in these native-resistant ones. Finally, the different mechanisms might be operative between acquired- and native-resistant tumor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Base Sequence
  • Blotting, Northern
  • Camptothecin / analogs & derivatives*
  • Camptothecin / pharmacology
  • Cell Division / drug effects
  • Cell Line
  • DNA Topoisomerases, Type I / genetics*
  • DNA Topoisomerases, Type I / metabolism
  • Drug Resistance / genetics
  • Gene Expression / drug effects
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Irinotecan
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Pancreatic Neoplasms
  • Polymerase Chain Reaction / methods
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Oligodeoxyribonucleotides
  • RNA, Messenger
  • Irinotecan
  • DNA Topoisomerases, Type I
  • Camptothecin