Immunohistochemically demonstrated variation in expression of cathepsin E between uracil-induced papillomatosis and N-butyl-N-(4-hydroxybutyl)nitrosamine-induced preneoplastic and neoplastic changes in rat urinary bladder.
Expression of rat urinary bladder cathepsin E in benign papillomatosis induced by uracil and various stages of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced carcinogenesis was investigated immunohistochemically. Seven-week-old, male F344/DuCrj rats were used. In the normal urothelium of control rats, cathepsin E stained in all layers of cells, although in umbrella cells and some basal cells the reaction was relatively weak. In rats given a diet containing 3% uracil for 5 weeks immunoreactivity of cathepsin E in uracil-induced papillomatosis was consistently homogeneous in all layers, but weaker than in normal urothelium. In rats given 0.05% BBN in drinking water for 12 weeks and subsequently maintained without treatment for 48 weeks cells with little cathepsin E, never observed in normal urothelium, appeared at 5 weeks above the basement membrane in the earliest stage of BBN-induced urinary bladder cancer (simple hyperplasia). Throughout the neoplastic process, groups of cells with a little cathepsin E were randomly distributed, with expression in the urothelium being markedly unstable. Almost all areas of squamous cell proliferation in TCC were negative for cathepsin E. Instability of cathepsin E expression in rat urothelium therefore appears characteristic for carcinogenesis and offers the possibility of using this feature as an early biomarker for urinary bladder carcinogenesis.
Yamamoto
S
S
Laboratory of Pathology, Aichi Cancer Center Research Institute, Nagoya, Japan.
Yonezawa
S
S
Ichinose
M
M
Miki
K
K
Masui
T
T
Fukushima
S
S
Inoue
H
H
Tatematsu
M
M
D000818:Animals; D002085:Butylhydroxybutylnitrosamine; D002273:Carcinogens; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced / Q000201:enzymology*; D020059:Cathepsin E; D002403:Cathepsins / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology; D010212:Papilloma / Q000139:chemically induced / Q000201:enzymology*; D051381:Rats; D011916:Rats, Inbred F344; D014498:Uracil; D001743:Urinary Bladder / Q000201:enzymology*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000201:enzymology*
D002273:Carcinogens; D009363:Neoplasm Proteins; D002085:Butylhydroxybutylnitrosamine; D014498:Uracil; D002403:Cathepsins; D020059:Cathepsin E