Oncogenic Potential of Bisphenol A and Common Environmental Contaminants in Human Mammary Epithelial Cells

被引:28
作者
Nair, Vidhya A. [1 ]
Valo, Satu [2 ]
Peltomaki, Paeivi [2 ]
Bajbouj, Khuloud [1 ]
Abdel-Rahman, Wael M. [1 ,3 ]
机构
[1] Univ Sharjah, Sharjah Inst Med Res, POB 27272, Sharjah, U Arab Emirates
[2] Univ Helsinki, Dept Med & Clin Genet, FI-00014 Helsinki, Finland
[3] Univ Sharjah, Coll Hlth Sci, Dept Med Lab Sci, POB 27272, Sharjah, U Arab Emirates
关键词
bisphenol A; breast cancer; hexabromocyclododecane; methoxychlor; nonylphenol; octylphenol; ESTROGEN-RECEPTOR-ALPHA; CANCER CELLS; BACTERIAL HEAT-SHOCK-PROTEIN-60; DNA METHYLATION; BREAST; HEXABROMOCYCLODODECANE; GROWTH; COLON; CARCINOGENESIS; TRANSCRIPTION;
D O I
10.3390/ijms21103735
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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, AMPK alpha 1, FAK, p53, GSK-3 alpha/beta, 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.
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页数:16
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