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TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
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Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
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Isolation, Culture, and Characterization of Prostate Cancer-Associated Fibroblasts
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The FOXF2 pathway in the human prostate stroma.

Leonie van der Heul-Nieuwenhuijsen1, Natasja Dits, Wilfred Van Ijcken

  • 1Department of Urology, Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands.

The Prostate
|June 30, 2009
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Summary

Forkhead box 2 (FOXF2) is decreased in prostate cancer and regulates stromal cell gene expression. This suggests FOXF2 plays a role in prostate homeostasis and interactions between stroma and epithelial cells.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Oncology

Background:

  • Forkhead box 2 (FOXF2) is a transcription factor with expression patterns suggesting a role in prostate cancer development.
  • FOXF2 is stroma-specific, more abundant in the prostate transition zone, and decreased in prostate cancer.
  • Its specific expression pattern indicates potential involvement in prostate stromal biology.

Purpose of the Study:

  • To identify genes and signaling pathways regulated by FOXF2 in prostate stromal cells.
  • To understand the molecular mechanisms underlying FOXF2's role in prostate stroma.

Main Methods:

  • Microarray expression profiling of primary prostate stromal cells (PrSC) treated with FOXF2 siRNA or control siRNA.
  • Validation of differentially expressed genes using RT-PCR.
  • Pathway analysis using Ingenuity Pathway Analysis and Gene Set Enrichment Analysis (GSEA).

Main Results:

  • Microarray analysis identified 190 differentially expressed genes regulated by FOXF2.
  • Genes downregulated by FOXF2 include MT1E, MT1F, PDGFA, ITGB1, and PSG7.
  • Genes upregulated by FOXF2 include WASF2, BAMBI, and CXCL12, impacting pathways like PPAR, PDGF, and ECM signaling.
  • FOXF2-upregulated genes were found to be downregulated by TGFbeta3, indicating an opposing role.

Conclusions:

  • FOXF2's distinct expression and regulation of ECM signaling suggest a role in prostate homeostasis.
  • FOXF2 influences stroma-epithelial interactions within the prostate.
  • The opposing role in the TGFbeta3 pathway highlights FOXF2's complex regulatory functions in the prostate.