Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) induce epigenetic alterations and promote human breast cell carcinogenesis in vitro.

Content Provider	Europe PMC
Author	Pierozan, Paula Cattani, Daiane Karlsson, Oskar
Abstract	Gene–environment interactions are involved in the development of breast cancer, the tumor type that accounts for the majority of the cancer-related deaths among women. Here, we demonstrate that exposure to PFOS (10 µM) and PFOA (100 µM)—two contaminants ubiquitously found in human blood—for 72 h induced breast epithelial cell (MCF-10A cell line) proliferation and alteration of regulatory cell-cycle proteins (cyclin D1, CDK6, p21, p53, p27, ERK 1/2 and p38) that persisted after a multitude of cell divisions. The contaminants also promoted cell migration and invasion by reducing the levels of E-cadherin, occludin and β-integrin in the unexposed daughter cells. The compounds further induced an increase in global DNA methylation and differentially altered histone modifications, epigenetic mechanisms implicated in tumorigenesis. This mechanistic evidence for PFOS- and PFOA-induced malignant transformation of human breast cells supports a role of these abundant contaminants in the development and progression of breast cancer. Increased knowledge of contaminant-induced effects and their contribution to breast tumorigenesis is important for a better understanding of gene–environment interactions in the etiology of breast cancer.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC7603464&blobtype=pdf
ISSN	03405761
Journal	Archives of Toxicology [Arch Toxicol]
Volume Number	94
DOI	10.1007/s00204-020-02848-6
PubMed Central reference number	PMC7603464
Issue Number	11
PubMed reference number	32700164
e-ISSN	14320738
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2020-07-22
Publisher Place	Berlin/Heidelberg
Access Restriction	Open
Rights License	Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2020
Subject Keyword	PFOS PFOA Cell transformation Cyclin D1 p21 Histone modification DNA methylation
Content Type	Text
Resource Type	Article
Subject	Health, Toxicology and Mutagenesis Medicine Toxicology