Expression of Estrogen Receptor beta Increases Integrin alpha 1 and Integrin beta 1 Levels and Enhances Adhesion of Breast Cancer Cells

Estrogen effects on mammary gland development and differentiation are mediated by two receptors (ER alpha and ER beta). Estrogen-bound ER alpha induces proliferation of mammary epithelial and cancer cells, while ER beta is important for maintenance of the differentiated epithelium and inhibits proliferation in different cell systems. In addition, the normal breast contains higher ER beta levels compared to the early stage breast cancers, suggesting that loss of ER beta could be important in cancer development. Analysis of ER beta-/- mice has consistently revealed reduced expression of cell adhesion proteins. As such, ER beta is a candidate modulator of epithelial homeostasis and metastasis. Consequently, the aim of this study was to analyze estrogenic effects on adhesion of breast cancer cells expressing ER alpha and ER beta. As ER beta is widely found in breast cancer but not in cell lines, we used ER alpha positive T47-D and MCF-7 human breast cancer cells to generate cells with inducible ER beta expression. Furthermore, the colon cancer cell lines SW480 and HT-29 were also used. Integrin alpha 1 mRNA and protein levels increased following ER beta expression. Integrin beta 1-the unique partner for integrin alpha 1-increased only at the protein level. ER beta expression enhanced the formation of vinculin containing focal complexes and actin filaments, indicating a more adhesive potential. This was confirmed by adhesion assays where ER beta increased adhesion to different extracellular matrix proteins, mostly laminin. In addition, ER beta expression was associated to less cell migration. These results indicate that ER beta affects integrin expression and clustering and consequently modulates adhesion and migration of breast cancer cells. J. Cell. Physiol. 222: 156-167, 2010. (C) 2009 Wiley-Liss, Inc.