title: Estrogen receptor beta modulates breast cancer cells functional properties, signaling and expression of matrix molecules.
abstract: Estrogen receptors have pivotal roles in breast cancer growth and progression. ERα has been clearly shown to play key role in hormone-dependent breast cancer properties, but little is known for the isoform ERβ. To evaluate the role of ERβ, we established stably transfected ERβ-suppressed MDA-MB-231 breast cancer cells by knocking down the human ERβ gene, using specific shRNA lentiviral particles. As observed by scanning electron microscopy, the ERβ suppression induces significant phenotypic changes in these cells, as compared to the control cells. Notably, the down-regulation of ERβ decreases the expression of the mesenchymal markers fibronectin and vimentin, whereas it increases the expression levels of the epithelial marker E-cadherin and cell junctions. These alterations are followed by reduced levels of the functional cell properties that promote the aggressiveness of these cells, such as proliferation, migration, spreading capacity, invasion and adhesion on collagen I. Notably, the down-regulation of ERβ reduces the migration of breast cancer cells through the tyrosine kinase receptors EGFR/IGF-IR and the JAK/STAT signaling pathways. Moreover, ERβ has a crucial role on the gene expression of several matrix mediators, including the proteoglycans syndecans-2/-4 and serglycin, several matrix metalloproteinases, plasminogen activation system components and receptor tyrosine kinases. These data clearly show that ERβ plays a crucial role in the cell behavior and ECM composition of the highly aggressive MDA-MB-231 cells and opens a new area of research to further understand its role and to improve pharmaceutical targeting of the non-hormone dependent breast cancer.
authors.affiliation: Biochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece; Foundation for Research and Technology-Hellas (FORTH), Patras, Greece.
authors.forename: Zoi
authors.initials: Z
authors.lastname: Piperigkou
authors.affiliation: Biochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Bouris
authors.affiliation: Department of Biomedical Sciences, University of Padova, Padova, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Onisto
authors.affiliation: Department for Life Quality Studies, University of Bologna, Rimini, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Franchi
authors.affiliation: Laboratory of Cell Proliferation and Ageing, Institute of Biology, N.C.S.R. "Demokritos", Athens, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Kletsas
authors.affiliation: Biochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece.
authors.forename: Achilleas D
authors.initials: AD
authors.lastname: Theocharis
authors.affiliation: Biochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece; Foundation for Research and Technology-Hellas (FORTH), Patras, Greece. Electronic address: n.k.karamanos@upatras.gr.
authors.forename: Nikos K
authors.initials: NK
authors.lastname: Karamanos
mesh_terms: D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D047629:Estrogen Receptor beta / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D020935:MAP Kinase Signaling System; D011509:Proteoglycans / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism
chemical_list: C000600034:ESR2 protein, human; D047629:Estrogen Receptor beta; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D017978:Receptors, Growth Factor
keywords: Breast cancer; Epithelial to mesenchymal transition; Estrogen receptor; Estrogen receptor beta