Unstable expression of the multi-drug-resistant phenotype in Chinese hamster ovary cells resistant to okadaic acid

Hiroko Tohda, Masashi Takao, Akihiko Kikuchi, Takeshi Yasumoto, Akira Yasui

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

A Chinese hamster ovary cell line resistant to okadaic acid (OA), OAR2-3 has a mutation of the protein phosphatase (PP) 2Aα gene and expresses a multi-drug resistance (MDR) phenotype. In the present work, we isolated two additional OA-resistant variants, also showing MDR with a cross-resistance profile similar to that of OAR2-3, and with increased and decreased expressions of the P-glycoprotein (Pgp) and DNA topoisomerase (topo) II protein, respectively. Unlike OAR2-3, however, they had no mutation in the same region of the PP2Aα gene. Except for OA-resistance in OAR2-3, the MDR was found to decrease in the absence of OA, and this decrease was again associated with changes in topo II- and Pgp-expressions. Thus, we conclude that 1) OA regulates the expressions of Pgp and topo II positively and negatively, respectively, resulting in reversible expression of MDR irrespective of genetic changes and 2) in OAR2-3, the mutation in the PP2Aα gene confers stable resistance to OA. The MDR was also linked with collateral sensitivity to some drugs, like cisplatin and nitrogen mustard.

Original languageEnglish
Pages (from-to)398-402
Number of pages5
JournalBiochemical and biophysical research communications
Volume232
Issue number2
DOIs
Publication statusPublished - 1997 Mar 17

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Unstable expression of the multi-drug-resistant phenotype in Chinese hamster ovary cells resistant to okadaic acid'. Together they form a unique fingerprint.

  • Cite this