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

研究成果: Article査読

9 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)398-402
ページ数5
ジャーナルBiochemical and biophysical research communications
232
2
DOI
出版ステータスPublished - 1997 3 17

ASJC Scopus subject areas

  • 生物理学
  • 生化学
  • 分子生物学
  • 細胞生物学

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