Abstract
There is an ample epidemiological evidence to support the role of environmental contaminants such as bisphenol A (BPA) in breast cancer development but the molecular mechanisms of their action are still not fully understood. Therefore, we sought to analyze the effects of three common contaminants (BPA; 4-tert-octylphenol, OP; hexabromocyclododecane, HBCD) on mammary epithelial cell (HME1) and MCF7 breast cancer cell line. We also supplied some data on methoxychlor, MXC; 4-nonylphenol, NP; and 2-amino-1-methyl-6-phenylimidazo [4–b] pyridine, PhIP. We focused on testing the prolonged (two months) exposure to low nano-molar concentrations (0.0015–0.0048 nM) presumed to be oncogenic and found that they induced DNA damage (evidenced by upregulation of pH2A.X, pCHK1, pCHK2, p-P53) and disrupted the cell cycle. Some agents induced epigenetic (methylation) changes of tumor suppressor genes TIMP3, CHFR, ESR1, IGSF4, CDH13, and GSTP1. Obviously, the accumulation of these molecular alterations is an essential base for cancer development. Consistent with this, we observed that these agents increased cellular invasiveness through collagen. Cellular abilities to form colonies in soft agar were increased for MCF7. Toxic agents induced phosphorylation of protein kinase such as EGFR, CREB, STAT6, c-Jun, STAT3, HSP6, HSP27, AMPKα1, FAK, p53, GSK-3α/β, and P70S6 in HME1. Most of these proteins are involved in potential oncogenic pathways. Overall, these data clarify the molecular alterations that can be induced by some common environmental contaminants in mammary epithelial cells which could be a foundation to understand environmental carcinogenesis.
Highlights
Breast cancer incidence has been generally rising over the last 50 years with rapid increases observed in developing countries [1,2,3]
Studies showed that women who migrate from low incidence to high incidence environment tend to develop breast cancer at higher rate than before supporting the hypothesis that breast cancer risk is strongly associated with environmental factors [5,6]
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Summary
Breast cancer incidence has been generally rising over the last 50 years with rapid increases observed in developing countries [1,2,3]. Developing countries show a higher incidence of breast cancer in urban compared to rural areas [4]. Studies showed that women who migrate from low incidence to high incidence environment tend to develop breast cancer at higher rate than before supporting the hypothesis that breast cancer risk is strongly associated with environmental factors [5,6]. Environmental exposures include other contaminants of our food and drink such as the common food carcinogen 2-amino-1-methyl-6-phenylimidazo [4–b] pyridine (PhIP) which is a heterocyclic amine formed during the high-temperature cooking of meat and is known as a “cooked-meat mutagen” [8,9,10]
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