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

K. Nishio, Yoshikazu Sugimoto, K. Kasahara, Y. Fujiwara, S. Nishiwaki, H. Fujiki, M. Ohata, N. Saijo

Research output: Contribution to journalArticle

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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-resistance. 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
Publication statusPublished - 1992
Externally publishedYes

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Phosphoproteins
Cisplatin
Lung Neoplasms
Phosphorylation
Okadaic Acid
Nuclear Proteins
Phosphoprotein Phosphatases
Protein Kinase C
Polyacrylamide Gel Electrophoresis
Proteins
Carcinogens
Esters
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Increased phosphorylation of nuclear phosphoproteins in human lung-cancer cells resistant to cis-diamminedichloroplatinum (II). / Nishio, K.; Sugimoto, Yoshikazu; Kasahara, K.; Fujiwara, Y.; Nishiwaki, S.; Fujiki, H.; Ohata, M.; Saijo, N.

In: International Journal of Cancer, Vol. 50, No. 3, 1992, p. 438-442.

Research output: Contribution to journalArticle

Nishio, K, Sugimoto, Y, Kasahara, K, Fujiwara, Y, Nishiwaki, S, Fujiki, H, Ohata, M & Saijo, N 1992, 'Increased phosphorylation of nuclear phosphoproteins in human lung-cancer cells resistant to cis-diamminedichloroplatinum (II)', International Journal of Cancer, vol. 50, no. 3, pp. 438-442.
Nishio, K. ; Sugimoto, Yoshikazu ; Kasahara, K. ; Fujiwara, Y. ; Nishiwaki, S. ; Fujiki, H. ; Ohata, M. ; Saijo, N. / Increased phosphorylation of nuclear phosphoproteins in human lung-cancer cells resistant to cis-diamminedichloroplatinum (II). In: International Journal of Cancer. 1992 ; Vol. 50, No. 3. pp. 438-442.
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AU - Fujiwara, Y.

AU - Nishiwaki, S.

AU - Fujiki, H.

AU - Ohata, M.

AU - Saijo, N.

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