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Basic FGF downregulates TSP50 expression via the ERK/Sp1 pathway

Miao Wang1, Yong-Li Bao, Yin Wu

  • 1National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China.

Journal of Cellular Biochemistry
|May 28, 2010
PubMed

Insights

Basic fibroblast growth factor (bFGF) downregulates testes-specific protease 50 (TSP50) expression by activating the ERK/Sp1 pathway. This finding offers insights into TSP50 regulation for breast cancer therapy.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Testes-specific protease 50 (TSP50) expression is elevated in breast cancer, promoting tumorigenesis.
  • Understanding TSP50's regulatory mechanisms is crucial for developing targeted tumor therapies.

Purpose of the Study:

  • To elucidate the mechanism by which basic fibroblast growth factor (bFGF) downregulates TSP50 expression.
  • To identify the signaling pathway involved in bFGF-mediated TSP50 transcriptional regulation.

Main Methods:

  • Utilized MDA-MB-231 and HEK293T cell lines.
  • Employed RT-PCR and promoter activity assays.
  • Investigated the roles of ERK and Sp1 signaling pathways, including inhibitor and dominant-negative mutant analyses.

Main Results:

  • bFGF downregulates TSP50 expression transcriptionally.
  • bFGF induces the phosphorylation of ERK and Sp1.
  • The ERK/Sp1 pathway is essential for bFGF-mediated TSP50 downregulation, with a key Sp1 site identified on the TSP50 promoter.

Conclusions:

  • bFGF downregulates TSP50 expression via the ERK-mediated phosphorylation of Sp1.
  • The identified bFGF/ERK/Sp1 signaling axis provides a potential therapeutic target for breast cancer treatment.

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