Neoplastic conversion of human urothelial cells in vitro by overexpression of H2O2-generating peroxisomal fatty acyl CoA oxidase.
An in vitro study was conducted to determine if malignant transformation can be induced in human urothelial cells immortalized with human papillomavirus E6/E7 genes. A clone designated 1T1 was isolated and then stably transfected with an acyl CoA oxidase (ACOX)-expression construct. The cells generated H2O2 in a large quantity from the substrate linoleic acid (LA). After 56 days of LA treatment, cells persistently formed an epithelial cyst in athymic nude mice with an occasional intracystic epithelial nodule. Our results indicate that human urothelial cells can be transformed to low grade neoplastic cells by H2O2 and suggest that H2O2 may be involved in the development of bladder cancer.
Tamatani
T
T
Department of Pathology, Northwestern University Medical School, Chicago, IL 60611-3008, USA.
Hattori
K
K
Nakashiro
K
K
Hayashi
Y
Y
Wu
S
S
Klumpp
D
D
Reddy
J K
JK
Oyasu
R
R
D042962:Acyl-CoA Oxidase; D000368:Aged; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D006861:Hydrogen Peroxide / Q000009:adverse effects / Q000378:metabolism*; D007621:Karyotyping; D019787:Linoleic Acid / Q000494:pharmacology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D020675:Peroxisomes / Q000201:enzymology*; D051381:Rats; D014162:Transfection; D019459:Urothelium / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*
D019787:Linoleic Acid; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; D042962:Acyl-CoA Oxidase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9