FGF Receptor 3FGF Receptor 3…and its role in Bladder Cancer…and its role in Bladder Cancer

Jenny EspinosaJenny EspinosaBiology 169Biology 169

March 30, 2004March 30, 2004

What is it?

Just what is FGFR3 anyway?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

Normally found in:Normally found in:

Rat

Zebrafish

Mouse

Frog

Fruitfly

As well as in…

US!!US!!

So what does it do??So what does it do??

Michiyuki Kanai, Mchael Goke, Shoji Tsunekawa and Daniel Podolsky

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

FGFR FGFR extracellular extracellular

domaindomain

FGFR intracellular domain

David M. Ornitz & Pierre J. Marie

Hmm… Hmm… what what happens then happens then if the cell is if the cell is mutated?mutated?

- Achondroplasia*

- Thanatophoric dysplasia*

- Non-syndromic cranial synostosis

- Crouzonodermoskeletal syndrome

- Hypochondroplasia*

Effects of activated Effects of activated FGFR3 in MiceFGFR3 in Mice

What role does it What role does it play play in in

CANCER ??CANCER ??

http://www.hollywoodurology.com/tcc.html

FGFR3 and Bladder Cancer

Bladder CancerBladder Cancer

– somatic mutation in bladder carcinomas somatic mutation in bladder carcinomas (superficial or low-grade)(superficial or low-grade)

– (74%) in non-invasive papillary tumors (74%) in non-invasive papillary tumors

– absence of mutations in carcinoma absence of mutations in carcinoma in situin situ

– recurrence more frequent in wild type FGFR3recurrence more frequent in wild type FGFR3

That’s all

folks!