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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzo(a)pyrene / toxicity*
  • Breast Neoplasms / chemically induced*
  • Breast Neoplasms / physiopathology
  • Carcinogens / toxicity*
  • Cell Movement / drug effects
  • Female
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • MAP Kinase Signaling System / physiology
  • Mammary Neoplasms, Animal / chemically induced*
  • Mammary Neoplasms, Animal / physiopathology
  • Matrix Metalloproteinase 9 / drug effects*
  • Matrix Metalloproteinase 9 / physiology
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness / physiopathology
  • Neoplasm Metastasis / physiopathology
  • Reactive Oxygen Species / metabolism
  • Reactive Oxygen Species / pharmacology*
  • Up-Regulation / drug effects


  • Carcinogens
  • Reactive Oxygen Species
  • Benzo(a)pyrene
  • Matrix Metalloproteinase 9