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Inorganic arsenite-induced malignant transformation of human prostate epithelial cells

  1. Author:
    Achanzar, W. E.
    Brambila, E. M.
    Diwan, B. A.
    Webber, M. M.
    Waalkes, M. P.

  2. Author Address

    NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, MD F0-09,111 Alexander Dr, Res Triangle Pk, NC 27709 USA NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA NCI, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21701 USA Michigan State Univ, Dept Med, E Lansing, MI 48824 USA Michigan State Univ, Dept Zool, E Lansing, MI 48824 USA Waalkes MP NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, MD F0-09,111 Alexander Dr, Res Triangle Pk, NC 27709 USA
    1. Year: 2002
  2. Journal: Journal of the National Cancer Institute
    1. 94
    2. 24
    3. Pages: 1888-1891
  4. Type of Article: Article
  1. 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 muM 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 firs; 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.

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External Sources

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  2. DOI: 10.1093/jnci/94.24.1888
  3. View record in Web of Science®
  4. WOS: 000179825200015

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