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The role of cadmium and nickel in estrogen receptor signaling and breast cancer: metalloestrogens or not?

Journal of environmental science and health. Part C, Environmental carcinogenesis & ecotoxicology reviews (2012-09-14)
Natalie B Aquino, Mary B Sevigny, Jackielyn Sabangan, Maggie C Louie
ABSTRACT

During the past half-century, incidences of breast cancer have increased globally. Various factors--genetic and environmental--have been implicated in the initiation and progression of this disease. One potential environmental risk factor that has not received a lot of attention is the exposure to heavy metals. While several mechanisms have been put forth describing how high concentrations of heavy metals play a role in carcinogenesis, it is unclear whether chronic, low-level exposure to certain heavy metals (i.e., cadmium and nickel) can directly result in the development and progression of cancer. Cadmium and nickel have been hypothesized to play a role in breast cancer development by acting as metalloestrogens--metals that bind to estrogen receptors and mimic the actions of estrogen. Since the lifetime exposure to estrogen is a well-established risk factor for breast cancer, anything that mimics its activity will likely contribute to the etiology of the disease. However, heavy metals, depending on their concentration, are capable of binding to a variety of proteins and may exert their toxicities by disrupting multiple cellular functions, complicating the analysis of whether heavy metal-induced carcinogenesis is mediated by the estrogen receptor. The purpose of this review is to discuss the various epidemiological, in vivo, and in vitro studies that show a link between the heavy metals, cadmium and nickel, and breast cancer development. We will particularly focus on the studies that test whether these two metals act as metalloestrogens in order to assess the strength of the data supporting this hypothesis.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Raney®-Nickel, W.R. Grace and Co. Raney® 2800, slurry, in H2O, active catalyst
Sigma-Aldrich
Nickel, nanopowder, <100 nm avg. part. size, ≥99% trace metals basis
Sigma-Aldrich
Nickel, foil, thickness 0.125 mm, ≥99.9%
Sigma-Aldrich
Nickel, powder, <150 μm, 99.99% trace metals basis
Sigma-Aldrich
Raney®-Nickel, W.R. Grace and Co. Raney® 2400, slurry, in H2O, active catalyst
Sigma-Aldrich
Nickel, foil, thickness 0.5 mm, 99.98% trace metals basis
Sigma-Aldrich
Nickel, wire, diam. 0.25 mm, ≥99.9%
Sigma-Aldrich
Nickel, foil, thickness 0.1 mm, 99.98% trace metals basis
Sigma-Aldrich
Nickel, wire, diam. 0.5 mm, ≥99.9% trace metals basis
Sigma-Aldrich
Nickel, wire, diam. 0.5 mm, ≥99.99% trace metals basis
Sigma-Aldrich
Nickel, rod, diam. 6.35 mm, ≥99.99% trace metals basis
Sigma-Aldrich
Nickel, foil, thickness 0.25 mm, 99.995% trace metals basis
Nickel, mesh, 100x250mm, nominal aperture 0.73mm, wire diameter 0.25mm, 26x26 wires/inch, open area 55%, plain weave mesh, 99%
Nickel, wire reel, 20m, diameter 0.025mm, as drawn, 99.98%
Nickel, wire reel, 10m, diameter 0.01mm, as drawn, 99.98%
Nickel, rod, 100mm, diameter 16mm, 99.99+%
Nickel, foil, not light tested, 100x100mm, thickness 0.01mm, 99.95%
Nickel, wire reel, 20m, diameter 0.125mm, hard, 99.98%
Nickel, rod, 100mm, diameter 3.0mm, 99%
Nickel, wire reel, 1m, diameter 1.0mm, hard, 99.98%
Nickel, broken cathode squares, 1000g, max. size 50mm, 99.8%
Nickel, tube, 1000mm, outside diameter 6.5mm, inside diameter 5.5mm, wall thickness 0.5mm, hard, 99.5%
Nickel, foil, 50mm disks, thickness 0.05mm, annealed, 99%
Nickel, wire reel, 20m, diameter 0.5mm, as drawn, 99%
Nickel, foil, 4mm disks, thickness 0.075mm, annealed, 99%
Nickel, foil, 4mm disks, thickness 0.075mm, as rolled, 99.98%
Nickel, foil, 4mm disks, thickness 0.125mm, annealed, 99%
Nickel, foil, 4mm disks, thickness 0.125mm, annealed, 99.98%
Nickel, foil, 4mm disks, thickness 0.125mm, as rolled, 100%
Nickel, foil, 4mm disks, thickness 0.125mm, as rolled, 99.99+%