Regulation of a multigenic invasion programme by the transcription factor, AP-1: re-expression of a down-regulated

I M Johnston1, H J Spence, J N Winnie

  • 1Beatson Institute for Cancer Research, CRC Beatson Laboratories, Bearsden, Glasgow.

Oncogene
|December 5, 2000
PubMed

Insights

The transcription factor AP-1 regulates genes involved in cell invasion during oncogenic transformation. Identifying these genes, like TSC-36/Frp, helps understand cancer progression and potential therapeutic targets.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • The transcription factor AP-1 (activator protein-1) is crucial for oncogene-induced cell transformation.
  • AP-1 functions downstream in the growth factor-Ras signal transduction pathway.
  • AP-1's role in regulating a multigenic invasion program during transformation was previously hypothesized.

Purpose of the Study:

  • To identify genes regulated by AP-1 in transformed cells.
  • To determine if these identified genes are involved in the cellular invasion process.

Main Methods:

  • Differential gene expression analysis using subtracted cDNA libraries.
  • Northern blot analysis to confirm differential gene expression.
  • Nucleic acid and amino acid sequence database searches.
  • Functional analysis of specific genes, including TSC-36/follistatin-related protein (TSC-36/Frp).

Main Results:

  • Subtracted cDNA libraries successfully identified up- and down-regulated genes in FBR-transformed fibroblasts.
  • Sequence analysis revealed that many identified genes encode proteins involved in cellular invasion.
  • Down-regulation of TSC-36/Frp was observed, and its re-expression inhibited in vitro invasion.

Conclusions:

  • AP-1 regulates a multigenic invasion program in transformed cells.
  • The identified AP-1-regulated genes are functionally linked to the invasion process.
  • TSC-36/Frp acts as an invasion suppressor, highlighting its role in the AP-1-mediated invasion program.

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