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.

Keywords::

• Estrogen receptor β
• breast cancer
• stable transfection
• GFP
• xenograft

Acknowledgments

The authors thank Dr. Guowei Gu (Calabria, Italy) for the gift of Plasmid pCMV5-hERβ. They are also grateful to Professor Tao Xi (Nanjing, China) for the gift of plasmid pEGFP-C3 and other supports during this study. They acknowledge the participation of Hong Zhou to some experiments during their graduate courses.

Declaration of interest

The study was supported by Natural Science Foundation Committee (NSFC 30672015, 30700779, 30800257, 30970776) and the major project from the Ministry of Science and Technology for new drug development (2009ZX09310-004).