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

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http://hdl.handle.net/10138/318400

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Nair , V A , Valo , S , Peltomäki , P , Bajbouj , K & Abdel-Rahman , W M 2020 , ' Oncogenic Potential of Bisphenol A and Common Environmental Contaminants in Human Mammary Epithelial Cells ' , International Journal of Molecular Sciences , vol. 21 , no. 10 , 3735 . https://doi.org/10.3390/ijms21103735

Julkaisun nimi: Oncogenic Potential of Bisphenol A and Common Environmental Contaminants in Human Mammary Epithelial Cells
Tekijä: Nair, Vidhya A.; Valo, Satu; Peltomäki, Päivi; Bajbouj, Khuloud; Abdel-Rahman, Wael M.
Tekijän organisaatio: Department of Medical and Clinical Genetics
University of Helsinki
Päiväys: 2020-05
Kieli: eng
Sivumäärä: 16
Kuuluu julkaisusarjaan: International Journal of Molecular Sciences
ISSN: 1422-0067
DOI-tunniste: https://doi.org/10.3390/ijms21103735
URI: http://hdl.handle.net/10138/318400
Tiivistelmä: 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.
Avainsanat: 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
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
Vertaisarvioitu: Kyllä
Tekijänoikeustiedot: cc_by
Pääsyrajoitteet: openAccess
Rinnakkaistallennettu versio: publishedVersion


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