Differential Na+,K(+)-ATPase activity and cisplatin sensitivity between transformants induced by H-ras and those induced by K-ras

Int J Cancer. 1994 Sep 1;58(5):672-7. doi: 10.1002/ijc.2910580510.

Abstract

We examined the differential effects of the H-ras oncogene and the K-ras oncogene on cisplatin sensitivity in murine NIH/3T3 cells transfected with these oncogenes. Although the NIH/3T3 cells transformed with H-ras oncogenes (EJ-NIH/3T3 and Ha8-21) showed an increased resistance to cisplatin compared to the parental NIH/3T3, the cell lines transformed with K-ras oncogenes (DT and 1,8DNP2-2-5) did not. Compared with NIH/3T3, the 2 H-ras transformants reduced both the accumulation of cisplatin and the Na+,K(+)-ATPase activity in the membrane fraction. On the other hand, we observed no significant difference in cellular accumulation of cisplatin or in Na+,K(+)-ATPase activity between parental NIH/3T3 and the K-ras transformants. Since these ras transformants did not affect the cellular metallothionein content, transcriptional level of DNA polymerase beta or activity of glutathione-S-transferase which is not associated with cisplatin sensitivity, these results suggest that cisplatin resistance is brought about by the H-ras oncogene, but not by K-ras, and that induction of cisplatin resistance by H-ras is mainly due to a reduction of cisplatin accumulation and an impairment of Na+,K(+)-ATPase activity in the membrane fraction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Cell Survival / drug effects
  • Cell Transformation, Neoplastic*
  • Cisplatin / metabolism
  • Cisplatin / pharmacology*
  • DNA Polymerase I / genetics
  • Genes, ras*
  • Glutathione Transferase / metabolism
  • Metallothionein / metabolism
  • Mice
  • Proto-Oncogene Proteins p21(ras) / genetics
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics
  • Sodium-Potassium-Exchanging ATPase / metabolism*

Substances

  • RNA, Messenger
  • RNA, Neoplasm
  • Metallothionein
  • Glutathione Transferase
  • DNA Polymerase I
  • Proto-Oncogene Proteins p21(ras)
  • Sodium-Potassium-Exchanging ATPase
  • Cisplatin