Expression of estrogen receptor beta increases integrin alpha1 and integrin beta1 levels and enhances adhesion of breast cancer cells.
Estrogen effects on mammary gland development and differentiation are mediated by two receptors (ERalpha and ERbeta). Estrogen-bound ERalpha induces proliferation of mammary epithelial and cancer cells, while ERbeta is important for maintenance of the differentiated epithelium and inhibits proliferation in different cell systems. In addition, the normal breast contains higher ERbeta levels compared to the early stage breast cancers, suggesting that loss of ERbeta could be important in cancer development. Analysis of ERbeta-/- mice has consistently revealed reduced expression of cell adhesion proteins. As such, ERbeta 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 ERalpha and ERbeta. As ERbeta is widely found in breast cancer but not in cell lines, we used ERalpha positive T47-D and MCF-7 human breast cancer cells to generate cells with inducible ERbeta expression. Furthermore, the colon cancer cell lines SW480 and HT-29 were also used. Integrin alpha1 mRNA and protein levels increased following ERbeta expression. Integrin beta1-the unique partner for integrin alpha1-increased only at the protein level. ERbeta expression enhanced the formation of vinculin containing focal complexes and actin filaments, indicating a more adhesive potential. This was confirmed by adhesion assays where ERbeta increased adhesion to different extracellular matrix proteins, mostly laminin. In addition, ERbeta expression was associated to less cell migration. These results indicate that ERbeta affects integrin expression and clustering and consequently modulates adhesion and migration of breast cancer cells.
Department of Biosciences and Nutrition, Novum, Karolinska Institutet, Huddinge, Stockholm, Sweden. karolina.lindberg@ki.se
Karolina
K
Lindberg
Anders
A
Ström
John G
JG
Lock
Jan-Ake
JA
Gustafsson
Lars-Arne
LA
Haldosén
Luisa A
LA
Helguero
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D047629:Estrogen Receptor beta / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D039423:Integrin alpha1 / Q000235:genetics / Q000378:metabolism*; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013752:Tetracycline / Q000494:pharmacology; D013997:Time Factors; D016596:Vinculin / Q000378:metabolism
D047629:Estrogen Receptor beta; D016326:Extracellular Matrix Proteins; D039423:Integrin alpha1; D019012:Integrin beta1; D012333:RNA, Messenger; D016596:Vinculin; D013752:Tetracycline