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Cadmium Malignantly Transforms Normal Human Breast Epithelial Cells into a Basal-like Phenotype

  1. Author:
    Benbrahim-Tallaa, L.
    Tokar, E. J.
    Diwan, B. A.
    Dill, A. L.
    Coppin, J. F.
    Waalkes, M. P.

  2. Author Address

    Benbrahim-Tallaa, Lamia, Tokar, Erik J.; Dill, Anna L.; Coppin, Jean-Francois, Waalkes, Michael P.] NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI,NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Diwan, Bhalchandra A.] SAIC Frederick Inc, Basic Sci Program, Frederick, MD USA.
    1. Year: 2009
  2. Journal: Environmental Health Perspectives
    1. 117
    2. 12
    3. Pages: 1847-1852
  4. Type of Article: Article
  5. ISSN: 0091-6765
  1. Abstract:

    BACKGROUND: Breast cancer has recently been linked to cadmium exposure. Although not uniformly supported, it is hypothesized that cadmium acts as a metalloestrogenic carcinogen via the estrogen receptor (ER). Thus, we studied the effects of chronic exposure to cadmium on the normal human breast epithelial cell line MCF-10A, which is ER-negative but can convert to ER-positive during malignant transformation. METHODS: Cells were continuously exposed to low-level cadmium (2.5 mu M) and checked in vitro and by xenograft study for signs of malignant transformation. Transformant cells were molecularly characterized by protein and transcript analysis of key genes in breast cancer. RESULTS: Over 40 weeks of cadmium exposure, cells showed increasing secretion of matrix metallo-proteinase-9, loss of contact inhibition, increased colony formation, and increasing invasion, all typical for cancer cells. Inoculation of cadmium-treated cells into mice produced invasive, metastatic anaplastic carcinoma with myoepithelial components. These cadmium-transformed breast epithelial (CTBE) cells displayed characteristics of basal-like breast carcinoma, including

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  2. DOI: 10.1289/ehp.0900999
  3. PMID: 20049202

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