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Fibroblast Growth Factors (FGFs)

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Fibroblast Growth Factors (FGFs). www-cryst.bioc.cam.ac.uk/ structure_gallery.html. Definition. According to General Practice Notebook: Fibroblast Growth Factor is a peptide with cellular communication abilities e.g. Stimulation of fibroblast and endothelial cell division

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fibroblast growth factors fgfs
Fibroblast Growth Factors (FGFs)
  • www-cryst.bioc.cam.ac.uk/ structure_gallery.html
definition
Definition
  • According to General Practice Notebook:
  • Fibroblast Growth Factor is a peptide with cellular communication abilities e.g.
      • Stimulation of fibroblast and endothelial cell division
      • Stimulation of angiogenesis
fgfs function in the cell
FGFs Function in the Cell
  • FGF is a ligand that binds to Fibroblast Growth Factor Receptors (FGFR), which in turn through tyrosine phosphorylation propagate signals through transduction pathway
cell lines
Cell Lines
  • FGFs induce mitogenic, chemotactic, and angiogenic activity
  • What effects does FGF have in the Mouse?
knock out mice
Knock-Out Mice
  • Dr. Miller et al, decided to knock-out:
      • FGF-1
      • FGF-2
      • Double Knock-out of FGF-1 and FGF-2
  • There results were:
there are 22 known fgfs
There are 22 known FGFs
  • It is thought that the redundancy among the 22 Fibroblast Growth Factors compensate for the knock-out of FGF-1 and FGF-2
angiogenesis is
Angiogenesis is:
  • The formation of new capillary blood vessels from pre-existing ones
        • Requires migration, proliferation and differentiation of endothelial cells into blood vessels
        • Plays an important role in wound healing
        • Plays an important role in cancer as well
tumor cells release angiogenic factors
Tumor Cells release angiogenic factors
  • Some scientist suggest that a tumor requires blood supply in order to grow beyond a few cubic millimeters
      • A tumor cell releases FGF and VEGF
      • As a result of receptor activation, endothelial cells will secrete proteases
      • The proteases digest basement membrane, which migrate and proliferate to form new blood vessels
fgf 3 int 2
FGF-3 (int-2)
  • Primarily expressed during development
  • First discovered in mouse mammary carcinogenesis
      • MMTV induces mammary tumors by acting as an insertional mutagen, and activating transcription of the nearby genes
      • FGF-3 (int) was found to be the site where the mouse mammary tumor virus (MMTV) usually integrates
mouse mammary tumor virus
Mouse Mammary Tumor Virus
  • Activates the promoter for FGF-3
      • This “turns on” FGF-3 at improper times during development
mmtv and human breast cancer
MMTV and Human Breast Cancer
  • Detectable MMTV env gene-related antigenic reactivity has been found in tissue sections of human breast cancer
  • The human homologue of the int-2 locus has been found to be amplified and expressed in 15% of the breast cancers
  • There are still no clear proof that the human homologs to MMTV are related to human breast cancer
breast cancer
Breast Cancer
  • Dr. Granato et al., researched the effects of FGFs in breast cancer
      • They concluded that bFGF (basic fibroblast growth factor) serum level is associated with the presence of breast cancer
      • They proposed that bFGF as a noninvasive diagnostic tool for breast cancer
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