title: Bisphenol A induces gene expression changes and proliferative effects through GPER in breast cancer cells and cancer-associated fibroblasts.
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.
  
  
  OBJECTIVE
  We studied the transduction signaling pathways through which BPA influences cell proliferation and migration in human breast cancer cells and cancer-associated fibroblasts (CAFs).
  
  
  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.
authors.affiliation: Department of Pharmaco-Biology, University of Calabria, Rende, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Pupo
authors.forename: Assunta
authors.initials: A
authors.lastname: Pisano
authors.forename: Rosamaria
authors.initials: R
authors.lastname: Lappano
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Santolla
authors.forename: Ernestina Marianna
authors.initials: EM
authors.lastname: De Francesco
authors.forename: Sergio
authors.initials: S
authors.lastname: Abonante
authors.forename: Camillo
authors.initials: C
authors.lastname: Rosano
authors.forename: Marcello
authors.initials: M
authors.lastname: Maggiolini
mesh_terms: D001559:Benzhydryl Compounds / Q000633:toxicity*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects*; D020868:Gene Silencing; D006801:Humans; D010636:Phenols / Q000633:toxicity*; D060888:Real-Time Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D010636:Phenols; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; C109584:GPER1 protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds