1. FGF Receptor 3 …and its role in Bladder Cancer Jenny Espinosa Biology 169 March 30, 2004 What is it?

2. Just what is FGFR3 anyway? Fibroblast Growth Factor Receptor 3  Receptor Tyrosine Kinase  Glycoprotein Contains extracellular immunoglobulin domains, a hydrophobic transmembrane domain, & a split tyrosine- kinase domain Two isoforms: FGFR3b and FGFR3c Found in the plasma membrane

3. Normally found in: Rat Zebrafish Mouse Frog Fruitfly As well as in…

4. US!!

5. So what does it do?? Michiyuki Kanai, Mchael Goke, Shoji Tsunekawa and Daniel Podolsky

6. Yeah, but what does it really do?! Involved in a developmental pathway Negative regulator of bone growth Promotion & inhibition of chondrocyte proliferation and differentiation (mouse) Regulation of epithelial cell growth & differentiation Involved in embryogenesis, angiogenesis, and wound healing Main point here… REGULATION OF CELL PROLIFERATION AND DIFFERENTIATION

7. FGFR extracellular domain FGFR intracellular domain David M. Ornitz & Pierre J. Marie Hmm… what happens then if the cell is mutated? - Achondroplasia* - Thanatophoric dysplasia* - Non-syndromic cranial synostosis - Crouzonodermoskeletal syndrome - Hypochondroplasia*

8. Effects of activated FGFR3 in Mice

9. What role does it play in CANCER ??

10. http://www.hollywoodurology.com/tcc.html FGFR3 and Bladder Cancer

11. Bladder Cancer –s–s–s–somatic mutation in bladder carcinomas (superficial or low-grade) –(–(–(–(74%) in non-invasive papillary tumors –a–a–a–absence of mutations in carcinoma in situ –r–r–r–recurrence more frequent in wild type FGFR3

12. That’s all folks!