Fibroblast Growth Factor 3 (FGF3) int-2 Brandon Williams成纤维细胞生长因子3（FGF3）int-2布兰登威廉姆斯.pptVIP

Fibroblast Growth Factor 3 (FGF3)int-2 Brandon Williams OBJECTIVES Biochemical Information Normal Function in Mouse Ear Development Breast Cancer and FGF3 EASY FACTS 22 FGFs in vertebrates FGF3: Chromosome 11 (humans) Fgf3: Chromosome 7 (mice) Are secreted polypeptides Use tyrosine kinase receptors for signaling Proto-oncogene FUNCTIONS Cell proliferation, migration, and differentiation during embryonic development Tissue repair, injury response in adults Angiogenesis FGF and Tyrosine Kinases FGFs bind to heparan sulfate and tyrosine kinase receptors (FGFRs) FGF binds to heparan sulfate FGF/heparan sulfate dimer binds to a FGFR Complexes form dimers Signal transduction FGFRs 7 prototypes from 4 genes 2 or 3 immunoglobulin-like extracellular domains Heparan sulfate binding domain Activated through autophosphorylation Signaling pathway includes Ras, Raf, SOS, etc. Receptor Dimerization FGFRs What Does FGF3 do in a wt Mouse? Mouse lives (viable) Inner ear problems Skeletal problems (tail) Mouse Ear Development FGF3 was thought to induce inner ear development McKay et al. showed that FGF3 is required for correct development of inner ear, not induction of otic placode Kreisler Mutant Mice Cannot be maintained as completely homozygous line (females do not breed and repeated outcrossing is needed to produce breeding stud males) Develop a otic placode etc. Inner ear is mutant FGF Expression Breast Cancer Numbers Most frequent cancer among women, other than skin cancer 203,500 new cases per year in U.S. 40,000 die each year 1 in 8 women 5% attributed to mutated BRCA1 FGF3 and Breast Cancer Mouse Mammary Tumor Virus (MMTV) Insertion of MMTV activates several genes including FGF3 that have been associated with breast cancer Mixed results Cyclin D is closely linked to FGF3 * 3/25/03 *