Fibroblast Growth Factors (FGFs)www-cryst.bioc.cam.ac.uk/ structure_gallery.html

DefinitionAccording to General Practice Notebook:Fibroblast Growth Factor is a peptide with cellular communication abilities e.g.Stimulation of fibroblast and endothelial cell divisionStimulation of angiogenesis

FGFs Function in the CellFGF is a ligand that binds to Fibroblast Growth Factor Receptors (FGFR), which in turn through tyrosine phosphorylation propagate signals through transduction pathway

Cell LinesFGFs induce mitogenic, chemotactic, and angiogenic activityWhat effects does FGF have in the Mouse?

Knock-Out MiceDr. Miller et al, decided to knock-out:FGF-1FGF-2Double Knock-out of FGF-1 and FGF-2

There results were:

Mouse Knock-outs had no major phenotypic variation from wild-typeWhy these results?

There are 22 known FGFsIt is thought that the redundancy among the 22 Fibroblast Growth Factors compensate for the knock-out of FGF-1 and FGF-2

Angiogenesis is:The formation of new capillary blood vessels from pre-existing onesRequires 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

Angiogenic Factors: FGF and VEGF

Tumor Cells release angiogenic factorsSome scientist suggest that a tumor requires blood supply in order to grow beyond a few cubic millimetersA tumor cell releases FGF and VEGFAs a result of receptor activation, endothelial cells will secrete proteasesThe proteases digest basement membrane, which migrate and proliferate to form new blood vessels

FGF-3 (int-2)Primarily expressed during developmentFirst 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 Activates the promoter for FGF-3This turns on FGF-3 at improper times during development

MMTV and Human Breast CancerDetectable MMTV env gene-related antigenic reactivity has been found in tissue sections of human breast cancerThe 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 CancerDr. 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 cancerThey proposed that bFGF as a noninvasive diagnostic tool for breast cancer

There are Elevated Levels of FGF in Breast Cancer Patients