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Toxicol Lett. 2015 May 5;234(3):201-10. doi: 10.1016/j.toxlet.2015.02.016. Epub 2015 Feb 24.

Effects of exposure to benzo[a]pyrene on metastasis of breast cancer are mediated through ROS-ERK-MMP9 axis signaling.

Author information

1
Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
2
Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China; Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing 100021, China. Electronic address: lxzhan@sibs.ac.cn.

Abstract

Metastasis is the leading cause of deaths in patients with breast cancer. Benzo[a]pyrene is a cumulative carcinogen and ubiquitous environmental pollutant with potent carcinogenic properties. As we report here, we established an accumulative mouse model mimicking the cumulative effects of benzo[a]pyrene exposure in human breast carcinogenesis. Our focus was on elucidating the mechanisms by which benzo[a]pyrene contributes to the process of breast cancer metastasis. Our study indicated that benzo[a]pyrene increased the migration of breast cancer cells both in vitro and in vivo. Specifically, we demonstrated that benzo[a]pyrene enhances breast cancer cell migration and invasion by up-regulating ROS-induced ERK signaling, leading to the activation of matrix metalloproteinases 9. Our results suggest that benzo[a]pyrene-induced mammary gland cancer metastasis is an important and intricate process facilitated by cumulative benzo[a]pyrene exposure leading to activation of the ROS-ERK-MMP9 signaling pathway.

KEYWORDS:

Benzo[a]pyrene; Breast cancer metastasis; ERK; MMP9; ROS

PMID:
25724548
DOI:
10.1016/j.toxlet.2015.02.016
[Indexed for MEDLINE]

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