Inhibitory effects of ERβ on proliferation, invasion, and tumor formation of MCF-7 breast cancer cells-prognostication for the use of ERβ-selective therapy

Abstract

Context: Estrogen is well-known as an important factor in the physiological functions and pathological processes of breast. Estrogen receptor β (ERβ) is expressed in the majority of breast cancers at lower levels compared with the normal breast tissue. Objective: The effect of ERβ on the characteristics of breast tumor cells and its prognostication for the use of ERβ-selective therapy were investigated here for the first time. Materials and methods: ERβ was overexpressed in ERα positive MCF-7 breast cancer cells by gene transfection. The proliferation, motility, and xenografts growth of MCF-7 cells were investigated by MTT assays, wound-healing assay and animal study. Results: Results demonstrated that ERβ-GFP localized in both the cytoplasm and the nucleus in the presence of 17β-estradiol (E2), with stronger fluorescence-signal intensity in the nucleus, 2.8-times higher than that in the cytoplasm. The ERβ overexpressed MCF-7 cells resulted in a 38.7% decreased growth rate and motility in vitro. Furthermore, ERβ overexpression enhanced the antiproliferative effects of phytoestrogen, antiestrogen, and histone deacetylase inhibitor. Exogenous ERβ expression reduced tumor volume by 99% at 27 days postadministration, indicated that overexpression of ERβ led to retardation of tumor formation and growth in immunodeficient mice. Discussion and conclusion: This study provided a relatively new evidence to support that ERβ is an important modulator of proliferation and motility of breast cancer cells, and implied for the first time a possibility for the use of novel ERβ-selective therapies in breast cancer treatment. © 2012 Informa Healthcare USA, Inc.