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A polycyclic aromatic hydrocarbon-enriched environmental chemical mixture enhances AhR, antiapoptotic signaling and a proliferative phenotype in breast cancer cells.

Publication ,  Journal Article
Gearhart-Serna, LM; Davis, JB; Jolly, MK; Jayasundara, N; Sauer, SJ; Di Giulio, RT; Devi, GR
Published in: Carcinogenesis
December 31, 2020

Emerging evidence suggests the role of environmental chemicals, in particular endocrine-disrupting chemicals (EDCs), in progression of breast cancer and treatment resistance, which can impact survival outcomes. However, most research tends to focus on tumor etiology and the effect of single chemicals, offering little insight into the effects of realistic complex mixture exposures on tumor progression. Herein, we investigated the effect of a polycyclic aromatic hydrocarbon (PAH)-enriched EDC mixture in a panel of normal and breast cancer cells and in a tumor organoid model. Cells or organoids in culture were treated with EDC mixture at doses estimated from US adult intake of the top four PAH compounds within the mixture from the National Health and Nutrition Examination Survey database. We demonstrate that low-dose PAH mixture (6, 30 and 300 nM) increased aryl hydrocarbon receptor (AhR) expression and CYP activity in estrogen receptor (ER) positive but not normal mammary or ER-negative breast cancer cells, and that upregulated AhR signaling corresponded with increased cell proliferation and expression of antiapoptotic and antioxidant proteins XIAP and SOD1. We employed a mathematical model to validate PAH-mediated increases in AhR and XIAP expression in the MCF-7 ER-positive cell line. Furthermore, the PAH mixture caused significant growth increases in ER-negative breast cancer cell derived 3D tumor organoids, providing further evidence for the role of a natural-derived PAH mixture in enhancing a tumor proliferative phenotype. Together, our integrated cell signaling, computational and phenotype analysis reveals the underlying mechanisms of EDC mixtures in breast cancer progression and survival.

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Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

December 31, 2020

Volume

41

Issue

12

Start / End Page

1648 / 1659

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Receptors, Aryl Hydrocarbon
  • Polycyclic Aromatic Hydrocarbons
  • Oncology & Carcinogenesis
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Female
  • Endocrine Disruptors
  • Cell Proliferation
  • Breast Neoplasms
 

Citation

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Gearhart-Serna, L. M., Davis, J. B., Jolly, M. K., Jayasundara, N., Sauer, S. J., Di Giulio, R. T., & Devi, G. R. (2020). A polycyclic aromatic hydrocarbon-enriched environmental chemical mixture enhances AhR, antiapoptotic signaling and a proliferative phenotype in breast cancer cells. Carcinogenesis, 41(12), 1648–1659. https://doi.org/10.1093/carcin/bgaa047
Gearhart-Serna, Larisa M., John B. Davis, Mohit Kumar Jolly, Nishad Jayasundara, Scott J. Sauer, Richard T. Di Giulio, and Gayathri R. Devi. “A polycyclic aromatic hydrocarbon-enriched environmental chemical mixture enhances AhR, antiapoptotic signaling and a proliferative phenotype in breast cancer cells.Carcinogenesis 41, no. 12 (December 31, 2020): 1648–59. https://doi.org/10.1093/carcin/bgaa047.
Gearhart-Serna LM, Davis JB, Jolly MK, Jayasundara N, Sauer SJ, Di Giulio RT, et al. A polycyclic aromatic hydrocarbon-enriched environmental chemical mixture enhances AhR, antiapoptotic signaling and a proliferative phenotype in breast cancer cells. Carcinogenesis. 2020 Dec 31;41(12):1648–59.
Gearhart-Serna, Larisa M., et al. “A polycyclic aromatic hydrocarbon-enriched environmental chemical mixture enhances AhR, antiapoptotic signaling and a proliferative phenotype in breast cancer cells.Carcinogenesis, vol. 41, no. 12, Dec. 2020, pp. 1648–59. Pubmed, doi:10.1093/carcin/bgaa047.
Gearhart-Serna LM, Davis JB, Jolly MK, Jayasundara N, Sauer SJ, Di Giulio RT, Devi GR. A polycyclic aromatic hydrocarbon-enriched environmental chemical mixture enhances AhR, antiapoptotic signaling and a proliferative phenotype in breast cancer cells. Carcinogenesis. 2020 Dec 31;41(12):1648–1659.
Journal cover image

Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

December 31, 2020

Volume

41

Issue

12

Start / End Page

1648 / 1659

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Receptors, Aryl Hydrocarbon
  • Polycyclic Aromatic Hydrocarbons
  • Oncology & Carcinogenesis
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Female
  • Endocrine Disruptors
  • Cell Proliferation
  • Breast Neoplasms