Download Fibroblast Growth Factors (FGFs)

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
Stimulation of angiogenesis
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
FGFs induce mitogenic, chemotactic, and angiogenic
activity
What effects does FGF have in the Mouse?
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:
Mouse Knock-outs had no major
phenotypic variation from wild-type
Why these results?
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:
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
Angiogenic Factors: FGF and
VEGF
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)
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
Activates the promoter for FGF-3
This “turns on” FGF-3 at improper times during development
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
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
There are Elevated Levels of FGF
in Breast Cancer Patients