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.