Inorganic arsenite-induced malignant transformation of human prostate epithelial cells.
Although several epidemiologic studies show an association between arsenic exposure and prostate cancer, it is still unknown whether human prostate epithelial cells are directly susceptible to arsenic-induced transformation. This study was designed to determine whether the nontumorigenic human prostate epithelial cell line RWPE-1 could be malignantly transformed in vitro by arsenite. RWPE-1 cells were continuously exposed to 5 micro M arsenite and monitored for signs of transformation, assessed as changes in matrix metalloproteinase-9 levels. After 29 weeks of exposure, the arsenite-exposed RWPE-1 cells (referred to as CAsE-PE) showed a marked increase in matrix metalloproteinase-9 secretion, a common finding in prostate malignancies. Malignant transformation was confirmed when CAsE-PE cells produced aggressive undifferentiated malignant epithelial tumors in nude mice. The tumors stained positive for human prostate-specific antigen, confirming their origin. These results are the first report of arsenite-induced malignant transformation of a human epithelial cell line and provide an important in vitro model for studying the mechanisms underlying arsenic-induced carcinogenesis in humans.
Achanzar
William E
WE
Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Brambila
Eduardo M
EM
Diwan
Bhalchandra A
BA
Webber
Mukta M
MM
Waalkes
Michael P
MP
D000818:Animals; D018053:Arsenites / Q000009:adverse effects*; D002273:Carcinogens / Q000009:adverse effects*; D002460:Cell Line / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D011467:Prostate / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000032:analysis; D019459:Urothelium / Q000187:drug effects / Q000473:pathology
D018053:Arsenites; D002273:Carcinogens; D017430:Prostate-Specific Antigen; D020780:Matrix Metalloproteinase 9; C015001:arsenite