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

ABSTRACT

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