ERβ exerts multiple stimulative effects on human breast carcinoma cells

Abstract

Recent studies of ERs in breast cancer have demonstrated the existence of ERβ in addition to ERα. Some clinical data indicated that ERβ had prognostic value for patient's survival, which suggested that ERβ plays a key role in breast cancer development and metastasis. To test this hypothesis, we generated an ERβ high-expression cell line by reintroduced human ERβ cDNA into MDA-MB-435 cells. We demonstrated that ERβ exerted multiple tumor-stimulative effects on human breast carcinoma cells both in vivo and in vitro. In in vitro studies, ERβ was able to increase the proliferation and invasion of MDA-MB-435 cells significantly, while these effects were totally estradiol independent. Also, this stimulation was characterized by downregulation of p21 and upregulation of MMP-9, as well as transcriptional factor Est-1. In in vivo studies, we also demonstrated that ERβ-transfected MDA-MB-435 cells grew much faster and had more pulmonary metastasis than mock or wild-type cells in nude mice. In ERβ-transfected MDA-MB-435 xenografts, ERβ caused significant reduction in p21 protein levels. Similar effects of ERβ on MMP-9 and Ets-1 expression noted in vitro studies were also observed in the in vivo studies. These in vitro and in vivo studies indicated that ERβ exerted multiple stimulative effects on breast cancer development and metastasis.