The cellular response to induction of the p21 c-Ha-ras oncoprotein includes stimulation of jun gene expression

L Sistonen, E Hölttä, T P Mäkelä, J Keski-Oja, K Alitalo

Research output: Contribution to journalArticleScientificpeer-review


We have studied the effects of c-Ha-ras oncogene in mouse NIH 3T3 fibroblasts by DNA transfection and analysis of gene expression at the mRNA and protein level in a heat- and heavy metal-inducible model system. The human c-Ha-ras proto-oncogene and oncogene were cloned under the hsp70 heat-shock promoter. Clonal lines of cells with negligible basal expression of the hsp-c-Ha-ras oncogene construct were chosen on the basis of the inducibility of p21c-Ha-ras protein and several transformation parameters. We demonstrate that the expression of ornithine decarboxylase (ODC) mRNA is enhanced approximately 4-6 h after the induction of the p21c-Ha-ras oncoprotein. This increase was reversible upon cessation of c-Ha-ras mRNA and protein synthesis, while constitutively elevated ODC was characteristic for stably c-Ha-ras-transformed cells. The high-level expression of ODC in ras-transformed cells was insensitive to tumour promoter stimulation. A similar mRNA induction by c-Ha-rasVal-12 was also observed for two other serum- and tumour promoter-regulated genes associated with the transformed phenotype: transin (stromelysin) and the glucose transporter. This prompted us to examine also potential changes in the expression of the serum- and tumour promoter-induced transcription factor genes junB and c-jun after induction of the hsp--c-Ha-ras construct. The junB mRNA was enhanced approximately 10-fold and the c-jun oncogene mRNA to a lesser degree in the hsp--c-Ha-ras-transfected cells after zinc activation of the hsp70 promoter. These effects were not seen in similarly treated control cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Original languageEnglish
Pages (from-to)815-22
Number of pages8
JournalEMBO Journal
Issue number3
Publication statusPublished - Mar 1989
MoE publication typeA1 Journal article-refereed


  • Animals
  • Cell Line, Transformed
  • Cloning, Molecular
  • DNA-Binding Proteins/biosynthesis
  • Gene Expression Regulation
  • Heat-Shock Proteins/genetics
  • Humans
  • Matrix Metalloproteinase 3
  • Metalloendopeptidases/genetics
  • Mice
  • Monosaccharide Transport Proteins/genetics
  • Ornithine Decarboxylase/genetics
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins/biosynthesis
  • Proto-Oncogene Proteins c-jun
  • Proto-Oncogene Proteins p21(ras)
  • RNA, Messenger/biosynthesis
  • Tetradecanoylphorbol Acetate/pharmacology
  • Transcription Factors/biosynthesis


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