Bisphenol A induces gene expression changes and proliferative effects through GPER in breast cancer cells and cancer-associated fibroblasts

Marco Pupo, Assunta Pisano, Rosamaria Lappano, Maria Francesca Santolla, Ernestina Marianna de Francesco, Sergio Abonante, Camillo Rosano, Marcello Maggiolini

Research output: Contribution to journalArticle

Abstract

Background: Bisphenol A (BPA) is the principal constituent of baby bottles, reusable water bottles, metal cans, and plastic food containers. BPA exerts estrogen-like activity by interacting with the classical estrogen receptors (ERα and ERβ) and through the G protein-coupled receptor (GPR30/GPER). In this regard, recent studies have shown that GPER was involved in the proliferative effects induced by BPA in both normal and tumor cells. Objectives: We studied the transduction signaling pathways through which BPA influences cell proliferation and migration in human breast cancer cells and cancer-associated fibroblasts (CAFs). Methods and results: We used as a model system SKBR3 breast cancer cells and CAFs that lack the classical ERs. Specific pharmacological inhibitors and gene-silencing procedures were used to show that BPA induces the expression of the GPER target genes c-FOS, EGR-1, and CTGF through the GPER/EGFR/ERK transduction pathway in SKBR3 breast cancer cells and CAFs. Moreover, we observed that GPER is required for growth effects and migration stimulated by BPA in both cell types. Conclusions: Results indicate that GPER is involved in the biological action elicited by BPA in breast cancer cells and CAFs. Hence, GPER-mediated signaling should be included among the transduction mechanisms through which BPA may stimulate cancer progression.

Original languageEnglish
Pages (from-to)1177-1182
Number of pages6
JournalEnvironmental Health Perspectives
Volume120
Issue number8
DOIs
Publication statusPublished - Aug 2012

Keywords

  • Bisphenol A
  • Breast cancer cells
  • Cancer-associated fibroblasts
  • GPR30/GPER
  • Tumor microenvironment

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Public Health, Environmental and Occupational Health

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