Knockdown by shRNA identifies S249C mutant FGFR3 as a potential therapeutic target in bladder cancer

摘要: More than 60% of low-grade non-invasive papillary urothelial cell carcinomas contain activating point mutations fibroblast growth factor receptor 3 (FGFR3). The phenotypic consequences constitutive activation FGFR3 in bladder cancer have not been elucidated and further studies are required to confirm the inhibiting activity cells. We measured transcript levels demonstrated that were significantly more abundant low-stage grade tumours. identified a tumour line, 97-7, expressing most common mutation (S249C) at similar In these cells, S249C protein formed stable homodimers was constitutively phosphorylated. used retrovirus-mediated delivery shRNA knockdown FGFR3. This induced flattening, decreased proliferation reduced clonogenicity on plastic soft agar. However, no effects wild-type observed telomerase immortalized normal human indicating possible dependence line mutant Re-expression shRNA-expressing 97-7 cells resulted reversal changes, confirming specificity shRNA. These results indicate targeted inhibition may represent useful therapeutic approach superficial cancer.