Inhibition of skeletal metastasis by ectopic ERα expression in ERα-negative human breast cancer cell lines

Abhik Bandyopadhyay, Long Wang, Hui Chin Shiau, Lu Zhe Sun

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Some hormone-independent breast cancers lack functional estrogen receptors (ERs) and show evidence of a more aggressive metastatic phenotype. A protective role of the ER has also been suggested in hormone-resistant breast cancer progression. In this study, we have investigated the effect of the ectopic expression of human ERα on the bone-metastatic potential of highly metastatic ERα-negative human breast cancer MDA-MB-231 and MDA-MB-435-F-L cell lines in an experimental model of bone metastasis in nude mice. ERα overexpression had no effect on the growth of both cell lines but reduced the expression of integrin αvβ3 and the receptor activator of NF-κB, which are known to promote bone metastasis. A significant reduction in the incidence of osteolytic bone metastasis was observed by X-ray imaging of the legs and arms of mice inoculated with ERα-expressing clones of MDA-MB-231 cells in comparison to controls. Ectopic expression of ERα in MDA-MB-435-F-L cells also reduced their widespread skeletal metastasis to the legs, arms, spine, and mandible, as detected by whole-mouse enhanced green fluorescent protein imaging. Our study indicates for the first time that stable reintroduction of functional ERα in ERα-negative human breast cancer cells can inhibit their aggressive bone-metastatic potential in an experimental bone metastasis model.

Original languageEnglish (US)
Pages (from-to)113-118
Number of pages6
JournalNeoplasia
Volume9
Issue number2
DOIs
StatePublished - Feb 2007

Keywords

  • Breast cancer
  • Estrogen receptor
  • Metastasis-related genes
  • Skeletal metastasis
  • Whole-mouse imaging

ASJC Scopus subject areas

  • Cancer Research

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