title: Inorganic arsenite-induced malignant transformation of human prostate epithelial cells.
abstract: 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.
authors.affiliation: Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Achanzar
authors.forename: Eduardo M
authors.initials: EM
authors.lastname: Brambila
authors.forename: Bhalchandra A
authors.initials: BA
authors.lastname: Diwan
authors.forename: Mukta M
authors.initials: MM
authors.lastname: Webber
authors.forename: Michael P
authors.initials: MP
authors.lastname: Waalkes
mesh_terms: 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
chemical_list: D018053:Arsenites; D002273:Carcinogens; D017430:Prostate-Specific Antigen; D020780:Matrix Metalloproteinase 9; C015001:arsenite