Inhibitory effects of ER{3 on proliferation, invasion, and tumor formation of MCF-7 breast cancer cells-prognostication for the use of ERP-selective therapy

摘要

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