Neoplastic transformation of rat thyroid cells requires the junB and fra-1 gene induction which is dependent on the HMGI-C gene product

EMBO J. 1997 Sep 1;16(17):5310-21. doi: 10.1093/emboj/16.17.5310.

Abstract

The expression of the high mobility group I (HMGI)-C chromatin component was shown previously to be essential for the establishment of the neoplastic phenotype in retrovirally transformed thyroid cell lines. To identify possible targets of the HMGI-C gene product, we have analyzed the AP-1 complex in normal, fully transformed and antisense HMGI-C-expressing rat thyroid cells. We show that neoplastic transformation is associated with a drastic increase in AP-1 activity, which reflects multiple compositional changes. The strongest effect is represented by the dramatic junB and fra-1 gene induction, which is prevented in cell lines expressing the antisense HMGI-C. These results indicate that the HMGI-C gene product is essential for the junB and fra-1 transcriptional induction associated with neoplastic transformation. The inhibition of Fra-1 protein synthesis by stable transfection with a fra-1 antisense RNA vector significantly reduces the malignant phenotype of the transformed thyroid cells, indicating a pivotal role for the fra-1 gene product in the process of cellular transformation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / genetics*
  • Gene Expression Regulation, Neoplastic
  • HMGA2 Protein
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / metabolism*
  • Protein Binding
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Proto-Oncogene Proteins c-jun / metabolism*
  • RNA, Antisense
  • RNA, Messenger / biosynthesis
  • RNA, Neoplasm / biosynthesis
  • Rats
  • Thyroid Gland / cytology
  • Thyroid Neoplasms / genetics*
  • Transcription Factor AP-1 / metabolism
  • Transcriptional Activation

Substances

  • HMGA2 Protein
  • High Mobility Group Proteins
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • RNA, Antisense
  • RNA, Messenger
  • RNA, Neoplasm
  • Transcription Factor AP-1
  • fos-related antigen 1