Perfluorooctanoic acid (PFOA) exposure promotes proliferation, migration and invasion potential in human breast epithelial cells

Arch Toxicol. 2018 May;92(5):1729-1739. doi: 10.1007/s00204-018-2181-4. Epub 2018 Mar 3.


Despite significant advances in early detection and treatment, breast cancer remains a major cause of morbidity and mortality. Perfluorooctanoic acid (PFOA) is a suspected endocrine disruptor and a common environmental pollutant associated with various diseases including cancer. However, the effects of PFOA and its mechanisms of action on hormone-responsive cells remain unclear. Here, we explored the potential tumorigenic activity of PFOA (100 nM-1 mM) in human breast epithelial cells (MCF-10A). MCF-10A cells exposed to 50 and 100 µM PFOA demonstrated a higher growth rate compared to controls. The compound promoted MCF-10A proliferation by accelerating G0/G1 to S phase transition of the cell cycle. PFOA increased cyclin D1 and CDK4/6 levels, concomitant with a decrease in p27. In contrast to previous studies of perfluorooctane sulfate (PFOS), the estrogen receptor antagonist ICI 182,780 had no effect on PFOA-induced cell proliferation, whereas the PPARα antagonist GW 6471 was able to prevent the MCF-10A proliferation, indicating that the underlying mechanisms involve PPARα-dependent pathways. Interestingly, we also showed that PFOA is able to stimulate cell migration and invasion, demonstrating its potential to induce neoplastic transformation of human breast epithelial cells. These results suggest that more attention should be paid to the roles of PFOA in the development and progression of breast cancer.

Keywords: Breast cancer; Cyclin D; EDCs; Endocrine disrupting chemicals; MCF-10A cells; P27.

MeSH terms

  • Breast Neoplasms / chemically induced
  • Breast Neoplasms / pathology
  • Caprylates / administration & dosage
  • Caprylates / toxicity*
  • Cell Cycle / drug effects
  • Cell Cycle / physiology
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cyclin D1 / metabolism
  • Dose-Response Relationship, Drug
  • Endocrine Disruptors / administration & dosage
  • Endocrine Disruptors / toxicity
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Female
  • Fluorocarbons / administration & dosage
  • Fluorocarbons / toxicity*
  • Humans
  • Mammary Glands, Human / cytology*
  • Mammary Glands, Human / drug effects
  • Oxazoles / pharmacology
  • PPAR alpha / antagonists & inhibitors
  • Receptors, Estrogen / metabolism
  • Tyrosine / analogs & derivatives
  • Tyrosine / pharmacology


  • CCND1 protein, human
  • Caprylates
  • Endocrine Disruptors
  • Fluorocarbons
  • GW 6471
  • Oxazoles
  • PPAR alpha
  • Receptors, Estrogen
  • Cyclin D1
  • Tyrosine
  • perfluorooctanoic acid