Accelerated induction of bladder cancer in patched heterozygous mutant mice.
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.
Hamed
Sahar
S
Laval University Cancer Research Centre, Centre Hospitalier Universitaire de Québec-L'Hôtel-Dieu de Québec, 11 Côte du Palais, Québec City, Québec G1R 2J6, Canada.
LaRue
Hélène
H
Hovington
Hélène
H
Girard
Johanne
J
Jeannotte
Lucie
L
Latulippe
Eva
E
Fradet
Yves
Y
D000818:Animals; D002085:Butylhydroxybutylnitrosamine / Q000633:toxicity; D002273:Carcinogens; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced / Q000235:genetics; D002455:Cell Division; D003043:Cocarcinogenesis; D017353:Gene Deletion; D005838:Genotype; D006579:Heterozygote; D020287:In Situ Nick-End Labeling; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D001743:Urinary Bladder / Q000502:physiology; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000235:genetics*
D002273:Carcinogens; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface; D002085:Butylhydroxybutylnitrosamine