Overexpression of members of the AP-1 transcriptional factor family from an early stage of renal carcinogenesis and inhibition of cell growth by AP-1 gene antisense oligonucleotides in the Tsc2 gene mutant (Eker) rat model

Biochem Biophys Res Commun. 1997 Dec 8;241(1):24-30. doi: 10.1006/bbrc.1997.7731.


We previously isolated subtracted cDNA clones for genes having increased expression in Tsc2 gene mutant (Eker) rat renal carcinomas (RCs). Among them, fra-1 encoding a transcriptional factor activator protein 1 (AP-1) was identified. We have therefore investigated whether other members of the AP-1 transcription factor family might also be involved in renal carcinogenesis in the Eker rat model. In the present study, overexpression of fra-1, fra-2, c-jun, junB, and junD mRNAs was demonstrated in RCs by Northern blot analysis. Interestingly, AP-1 proteins were highly expressed even in the earliest preneoplastic lesions (e.g., phenotypically altered tubules) as suggested by immunohistochemistry. Moreover, 12-O-tetradecanoylphorbol-13-acetate-responsive element (TRE)-binding activity of AP-1 proteins was observed in RC cell extracts by electrophoretic mobility shift assay. As a next step, we transfected antisense oligonucleotides targeting AP-1 genes into RC cells and demonstrated that their growth was strongly inhibited. Thus, the data suggest that overexpression of AP-1 genes might play a crucial role in renal carcinogenesis in the Eker rat model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology*
  • Cell Division / drug effects
  • DNA-Binding Proteins / biosynthesis
  • Fos-Related Antigen-2
  • Genes, Tumor Suppressor*
  • Kidney / metabolism
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology*
  • Male
  • Multigene Family
  • Neoplasm Staging
  • Oligonucleotides, Antisense / pharmacology*
  • Proto-Oncogene Proteins c-fos / biosynthesis
  • Proto-Oncogene Proteins c-jun / biosynthesis
  • Rats
  • Rats, Mutant Strains
  • Repressor Proteins / biosynthesis
  • Repressor Proteins / genetics*
  • Transcription Factor AP-1 / biosynthesis*
  • Transcription Factor AP-1 / genetics
  • Transcription Factors / biosynthesis
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins


  • DNA-Binding Proteins
  • Fos-Related Antigen-2
  • Fosl2 protein, rat
  • Oligonucleotides, Antisense
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • Repressor Proteins
  • Transcription Factor AP-1
  • Transcription Factors
  • Tsc2 protein, rat
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins