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

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