Urothelial tumorigenesis: a tale of divergent pathways

Nat Rev Cancer. 2005 Sep;5(9):713-25. doi: 10.1038/nrc1697.


Urothelial carcinoma of the bladder is unique among epithelial carcinomas in its divergent pathways of tumorigenesis. Low-grade papillary tumours rarely become muscle-invasive and they frequently harbour gene mutations that constitutively activate the receptor tyrosine kinase-Ras pathway. By contrast, most high-grade invasive tumours progress to life-threatening metastases and have defects in the p53 and the retinoblastoma protein pathways. Correcting pathway-specific defects represents an attractive strategy for the molecular therapy of urothelial carcinomas.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Carcinoma, Papillary / genetics*
  • Carcinoma, Transitional Cell / genetics*
  • Cell Transformation, Neoplastic / genetics*
  • Genes, Retinoblastoma
  • Genes, ras
  • Humans
  • Tumor Suppressor Protein p53 / genetics
  • Urinary Bladder Neoplasms / genetics*
  • Urothelium / pathology*


  • Tumor Suppressor Protein p53