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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 wild-type

    • 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: wild-type

    • 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 wild-type

    • 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) wild-type

    • 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 wild-type

    • 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 wild-type

    • 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 wild-type

    • 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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