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Transcriptional repression of fibroblast growth factor 8 by transforming growth factor-beta in androgen-dependent

Norio Takayashiki1, Hirotoshi Kawata, Tomoko Kamiakito

  • 1Department of Pathology, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi, Kawachi, Tochigi 329-0498, Japan.

The Journal of Steroid Biochemistry and Molecular Biology
|June 7, 2005
PubMed

Insights

Transforming growth factor-beta (TGF-beta) represses androgen-inducible fgf8 gene expression in mouse mammary carcinoma cells, suggesting TGF-beta controls androgen-responsive genes and inhibits cell growth by downregulating fgf8.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Androgen signaling pathways are crucial for the growth of certain cancers, including mouse mammary carcinoma SC-3 cells.
  • Transforming growth factor-beta (TGF-beta) is a pleiotropic cytokine involved in cell growth, differentiation, and apoptosis.
  • Understanding the interplay between TGF-beta and androgen signaling is important for cancer therapy.

Purpose of the Study:

  • To characterize the transcriptional profiles of TGF-beta-responsive genes in androgen-dependent mouse mammary carcinoma SC-3 cells.
  • To investigate the effect of TGF-beta on the expression of fgf8, an androgen-inducible growth factor.
  • To elucidate the mechanism of TGF-beta-mediated growth inhibition in SC-3 cells.

Main Methods:

  • Gene expression profiling using microarrays.
  • Quantitative real-time PCR (RT-PCR) to validate gene expression changes.
  • TUNEL assay and caspase 3 activity assay to assess apoptosis.
  • Flow cytometry to analyze cell cycle effects.
  • Reporter assays to study promoter activity.

Main Results:

  • TGF-beta treatment resulted in significant up-regulation (165 genes) and down-regulation (78 genes) of gene expression in SC-3 cells.
  • Expression of fgf8, essential for SC-3 cell growth, was severely repressed by TGF-beta.
  • TGF-beta induced cell stasis rather than apoptosis in SC-3 cells.
  • TGF-beta suppressed androgen-responsive promoter activity, indicating transcriptional control.

Conclusions:

  • TGF-beta represses the androgen-inducible fgf8 gene in mouse mammary carcinoma cells.
  • TGF-beta-mediated growth inhibition likely involves the repression of fgf8.
  • TGF-beta may directly or indirectly control the transcription of androgen-inducible genes, including fgf8.

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