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ERß Inhibits Proliferation and Invasion of Breast Cancer Cells

INSERM U540 "Molecular and Cellular Endocrinology of Cancers," 34090 Montpellier, France

Address all correspondence and requests for reprints to: Dr Françoise Vignon or Dr. Gwendal Lazennec, INSERM U540 "Molecular and Cellular Endocrinology of Cancers," 60 rue de Navacelles, 34090 Montpellier, France. u540.montp.inserm.fr or lazennec{at}u540.montp.inserm.fr

Recent studies indicate that the expression of ERß in breast cancer is lower than in the normal breast, suggesting that ERß could play an important role in carcinogenesis. To investigate this hypothesis, we engineered ER-negative MDA-MB-231 (human breast cancer cells) to reintroduce either ER or ERß protein with an adenoviral vector. In these cells, ERß (as ER) expression was monitored using RT-PCR and Western blot. ERß protein was localized in the nucleus (immunocytochemistry) and able to transactivate estrogen-responsive reporter constructs in the presence of E2. ERß and ER induced the expression of several endogenous genes such as pS2, TGF, or the cyclin kinase inhibitor p21 but, in contrast to ER, ERß was unable to regulate c-myc proto-oncogene expression. The pure antiestrogen ICI 164, 384 completely blocked ER and ERß estrogen-induced activities. ERß inhibited MDA-MB-231 cell proliferation in a ligand-independent manner, whereas ER inhibition of proliferation is hormone dependent. Moreover, ERß and ER decreased cell motility and invasion. Our data bring the first evidence that ERß is an important modulator of proliferation and invasion of breast cancer cells and support the hypothesis that the loss of ERß expression could be one of the events leading to the development of breast cancer.