Characterization of an Etoposide‐resistant Human K562 Cell Line, K/eto

Isamu Sugawara, Toshiro Iwahashi, Kazuya Okamoto, Yoshikazu Sugimoto, Hisao Ekimoto, Takashi Tsuruo, Tatsuro Ikeuchi, Shigeo Mori

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Abstract

An etoposide‐resistant K562 cell line (K/eto) was obtained by stepwise exposure, in culture, to increasing concentrations of etoposide, without the use of mutagens. This cell line was resistant to etoposide, and slightly resistant to adriamycin, but sensitive to anti‐cancer drugs such as camptothecin, vincristine, actinomycin D and so on. P‐GIycoprotein, the mdr1 gene product, was not detected in this cell line, as assessed by immunocytochemistry, itnmunoprecipitation and flow cytometry. Overexpression of mdr1 mRNA was also not found. Interestingly, expression of 85 kD protein recognized by MRK 20 monoclonal antibody was noted. The level of DNA topoisomerase II protein, detected by antibody staining, decreased concomitantly with a general decrease in DNA topoisomerase II unknotting activity, while DNA topoisomerase I activity was not affected. Cellular accumulation of [3H]etoposide was reduced by 75% in the resistant line compared with parental K562. Karyotype analysis showed that the number of chromosomes in K/eto was 55 and neither a homogeneous staining region nor double‐minute chromosomes were detected. These results indicate that this resistance is not due to an altered interaction between the drug and cellular transport machinery, i.e. MDR1, associated with the “classic” multiple drug resistance phenotype, but rather is due to the existence of other mechanism(s) of resistance, decreased transport of the drug and decreased target enzyme, DNA topoisomerase II.

Original languageEnglish
Pages (from-to)1035-1043
Number of pages9
JournalJapanese Journal of Cancer Research
Volume82
Issue number9
DOIs
Publication statusPublished - 1991 Sep

Keywords

  • 85 kD protein
  • DNA topoisomerase II
  • Etoposide
  • K562
  • Multidrug resistance

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Sugawara, I., Iwahashi, T., Okamoto, K., Sugimoto, Y., Ekimoto, H., Tsuruo, T., Ikeuchi, T., & Mori, S. (1991). Characterization of an Etoposide‐resistant Human K562 Cell Line, K/eto. Japanese Journal of Cancer Research, 82(9), 1035-1043. https://doi.org/10.1111/j.1349-7006.1991.tb01940.x