Increased phosphorylation of nuclear phosphoproteins in human lung‐cancer cells resistant to cis‐diamminedichloroplatinum(II)

Kazuto Nishio, Yoshikazu Sugimoto, Kazuo Kasahara, Yasuhiro Fujiwara, Shinji Nishiwaki, Hirota Fujiki, Masahiro Ohata, Nagahiro Saijo

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Abstract

A novel non‐phorbol‐ester‐like tumor promoter, okadaic acid (OA) has been shown to be an inhibitor of protein phosphatase I and IIA and, thus, to cause an “apparent activation” of protein kinase C (PKC). We previously showed that cis‐diamminedichloroplatinum(II) (CDDP)‐resistant cells, PC‐9/CDDP, were cross‐ resistant to OA and that the cross‐resistance was not due to the increased efflux of OA. We hypothesized that the phosphorylation status of some cellular proteins might be important in CDDP‐resistancc. No significant difference in PKC activity or total protein phosphatase activity measured in vitro was seen between PC‐9 and PC‐9/CDDP cells, nor in their sensitivity to inhibition by OA, nor in the amount of phosphorylation of whole cells or TCA‐insoluble material. By SDS‐PAGE after incubation of intact cells with 32P, we detected a marked increase, compared to PC‐9 cells, in phosphorylation of the nuclear proteins of MW 32 and 20 kDa in CDDP‐resistant PC‐9/CDDP cells with no apparent difference in protein content. When phosphorylation of nuclear proteins observed in PC‐9/CDDP cells was analyzed by 2‐dimensional SDS‐PAGE, the 32‐kDa protein had a PI of about 4.5. The 32‐kDa and 20‐kDa bands were increased in a dose‐dependent manner by CDDP treatment. On the other hand, no increase in phosphorylation of these proteins was observed in parental PC‐9 cells. These results demonstrate a marked difference in the phosphorylation status of specific nuclear proteins between parental and CDDP‐resistant cell lines, which may be related to CDDP‐resistance.

Original languageEnglish
Pages (from-to)438-442
Number of pages5
JournalInternational Journal of Cancer
Volume50
Issue number3
DOIs
Publication statusPublished - 1992 Feb 1

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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