Accelerated induction of bladder cancer in patched heterozygous mutant mice

Cancer Res. 2004 Mar 15;64(6):1938-42. doi: 10.1158/0008-5472.can-03-2031.

Abstract

The PATCHED (PTC) gene is recognized as a tumor suppressor in basal cell carcinoma. Mapping of a minimal region of deletion at 9q22.3 and observation of a decreased PTC expression in superficial papillary bladder tumors led us to hypothesize that it could also be involved in this cancer. To further investigate this hypothesis, we submitted Ptc(+/-) heterozygous mutant mice and their wild-type littermates to chemical carcinogenesis by adding N-butyl-N-(4-hydroxybutyl) nitrosamine to their drinking water. Preneoplastic and neoplastic changes were observed significantly earlier in the Ptc(+/-) than in the wild-type mice. Our data support the hypothesis of Ptc acting as a tumor suppressor gene in bladder cancer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Butylhydroxybutylnitrosamine / toxicity
  • Carcinogens
  • Carcinoma, Transitional Cell / chemically induced
  • Carcinoma, Transitional Cell / genetics
  • Cell Division
  • Cocarcinogenesis
  • Gene Deletion
  • Genotype
  • Heterozygote
  • In Situ Nick-End Labeling
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Membrane Proteins / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Patched Receptors
  • Patched-1 Receptor
  • Receptors, Cell Surface
  • Urinary Bladder / physiology
  • Urinary Bladder Neoplasms / chemically induced
  • Urinary Bladder Neoplasms / genetics*

Substances

  • Carcinogens
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Patched Receptors
  • Patched-1 Receptor
  • Ptch1 protein, mouse
  • Receptors, Cell Surface
  • Butylhydroxybutylnitrosamine