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

Pharm Biol. 2012 Jul;50(7):839-49. doi: 10.3109/13880209.2011.637506. Epub 2012 Apr 10.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Cell Line, Tumor
  • Cell Proliferation*
  • Estrogen Receptor beta / administration & dosage
  • Estrogen Receptor beta / physiology*
  • Estrogen Receptor beta / therapeutic use
  • Evidence-Based Medicine / methods
  • Female
  • Growth Inhibitors / administration & dosage
  • Growth Inhibitors / physiology*
  • Growth Inhibitors / therapeutic use
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness / pathology
  • Neoplasm Invasiveness / prevention & control
  • Prognosis
  • Xenograft Model Antitumor Assays / methods

Substances

  • Estrogen Receptor beta
  • Growth Inhibitors