Effects of methylmercury on breast cancer cells.
Metalloestrogens are small ionic metals that activate the estrogen receptor (ER). Studies have shown that when metalloestrogens bind to the ER there is an increase in the transcription and expression of estrogen-related genes, inducing proliferation of estrogen-dependent breast cancer. Mercury, a metalloestrogen, is a bivalent cation that is present in the environment. At high concentrations, mercury (Hg) is toxic and enhances production or reactive oxygen species (ROS), which are tightly regulated under normal oxidative environments. However, at lower concentrations mercury promotes a slight increase in ROS production. Here, cells were treated with methylmercury (MeHg), an organic Mercury compound, which has similar effects as Hg, but can more readily enter cells. Using mercury analysis to determine intracellular Hg concentrations, a protocol that maximizes cellular exposure to MeHg has been determined. The MeHg treatment led to the proliferation of ER-positive breast cancers while protecting cells from apoptotic signals at concentrations of 1 and 10 nM. Cell death was shown after treatment with concentrations of MeHg above 1 μM. It was shown that mercury-induced proliferation was absent in ER-negative breast cancer cells, suggesting that mercury-induced proliferation occurs via the ER. In support of this data, preliminary results suggest that pre-treatment of breast cancer cells with the pan-ER inhibitor ICI 182,780 may inhibit mercury's proliferative effects. Clarifying the effects of mercury, and its derivatives, on breast cancer may lead to a better understanding of how environmental toxins affect tumor progression and may lead to the development of future therapeutic strategies.
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