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Gwendal Lazennec, Damien Bresson, Annick Lucas, Corine Chauveau, Françoise Vignon, ERβ Inhibits Proliferation and Invasion of Breast Cancer Cells, Endocrinology, Volume 142, Issue 9, 1 September 2001, Pages 4120–4130, https://doi.org/10.1210/endo.142.9.8395
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Abstract
Recent studies indicate that the expression of ERβ in breast cancer is lower than in the normal breast, suggesting that ERβ 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 ERα or ERβ protein with an adenoviral vector. In these cells, ERβ (as ERα) expression was monitored using RT-PCR and Western blot. ERβ protein was localized in the nucleus (immunocytochemistry) and able to transactivate estrogen-responsive reporter constructs in the presence of E2. ERβ and ERα induced the expression of several endogenous genes such as pS2, TGFα, or the cyclin kinase inhibitor p21 but, in contrast to ERα, ERβ was unable to regulate c-myc proto-oncogene expression. The pure antiestrogen ICI 164, 384 completely blocked ERα and ERβ estrogen-induced activities. ERβ inhibited MDA-MB-231 cell proliferation in a ligand-independent manner, whereas ERα inhibition of proliferation is hormone dependent. Moreover, ERβ and ERα decreased cell motility and invasion. Our data bring the first evidence that ERβ is an important modulator of proliferation and invasion of breast cancer cells and support the hypothesis that the loss of ERβ expression could be one of the events leading to the development of breast cancer.
