Abstract
Cadmium is an omnipotent environmental contaminant associated with the development of breast cancer. Studies suggest that cadmium functions as an endocrine disruptor, mimicking the actions of estrogen in breast cancer cells and activating the receptor to promote cell growth. Although acute cadmium exposure is known to promote estrogen receptor-mediated gene expression associated with growth, the consequence of chronic cadmium exposure is unclear. Since heavy metals are known to bioaccumulate, it is necessary to understand the effects of prolonged cadmium exposure. This study aims to investigate the effects of chronic cadmium exposure on breast cancer progression. A MCF7 breast cancer cell line chronically exposed to 10−7 M CdCl2 serves as our model system. Data suggest that prolonged cadmium exposures result in the development of more aggressive cancer phenotypes – increased cell growth, migration and invasion. The results from this study show for the first time that chronic cadmium exposure stimulates the expression of SDF-1 by altering the molecular interactions between ERα, c-jun and c-fos. This study provides a mechanistic link between chronic cadmium exposure and ERα and demonstrates that prolonged, low-level cadmium exposure contributes to breast cancer progression.
Highlights
Breast cancer is one of the most common malignancies afflicting women in the United States, and it has the second highest mortality rate associated with any cancer
We previously found that acute cadmium exposures increase growth rates of three ERa-positive breast cancer cell lines– MCF7, T47D and ZR75-1– and increase the expression of genes associated with growth [8]
The observation that acute cadmium exposure stimulates breast cancer cell proliferation led us to question the effects of chronic cadmium exposure on breast cancer progression
Summary
Breast cancer is one of the most common malignancies afflicting women in the United States, and it has the second highest mortality rate associated with any cancer. The majority of breast cancers initially develop as hormone-dependent, with estrogen receptors expressed in approximately 70% of breast cancer cases. The presence or absence of ERa is a key determinant of the prognosis of the disease, in addition to determining whether the cancer will respond to hormone therapy or not. ERa-positive breast cancers are often hormone-responsive and are typically treated with antiestrogens like tamoxifen. Hormonedependent breast cancer frequently progresses into more malignant cancer phenotypes that are often hormone-independent. The estrogen receptor (ERa) is still present, but the role of ERa in hormone refractory breast tumorigenesis and its underlying mechanism are unclear. A potential mechanism involves metalloestrogens– heavy metals that function as endocrine disruptors and mimic the actions of estrogen
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