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

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 ERalpha on the bone-metastatic potential of highly metastatic ERalpha-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. ERalpha overexpression had no effect on the growth of both cell lines but reduced the expression of integrin alpha(v)beta(3) and the receptor activator of NF-kappaB, 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 ERalpha-expressing clones of MDA-MB-231 cells in comparison to controls. Ectopic expression of ERalpha 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 ERalpha in ERalpha-negative human breast cancer cells can inhibit their aggressive bone-metastatic potential in an experimental bone metastasis model.
AuthorsAbhik Bandyopadhyay, Long Wang, Shiau Hui Chin, Lu-Zhe Sun
JournalNeoplasia (New York, N.Y.) (Neoplasia) Vol. 9 Issue 2 Pg. 113-8 (Feb 2007) ISSN: 1476-5586 [Electronic] United States
PMID17356707 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Estrogen Receptor alpha
  • Estrogens
  • Integrin alphaVbeta3
  • NF-kappa B
  • Neoplasm Proteins
  • Receptor Activator of Nuclear Factor-kappa B
  • Recombinant Fusion Proteins
  • TNFRSF11A protein, human
  • Green Fluorescent Proteins
Topics
  • Adenocarcinoma (pathology, prevention & control, secondary)
  • Animals
  • Bone Neoplasms (prevention & control, secondary)
  • Breast Neoplasms (pathology)
  • Cell Line, Tumor (chemistry, pathology, transplantation)
  • Clone Cells (chemistry, pathology, transplantation)
  • Estrogen Receptor alpha (analysis, biosynthesis, genetics, physiology)
  • Estrogens
  • Female
  • Genes, Reporter
  • Green Fluorescent Proteins (analysis, genetics)
  • Humans
  • Integrin alphaVbeta3 (biosynthesis, genetics)
  • Lung Neoplasms (genetics, prevention & control, secondary)
  • Mice
  • Mice, Nude
  • NF-kappa B (metabolism)
  • Neoplasm Invasiveness
  • Neoplasm Proteins (analysis, biosynthesis, genetics)
  • Neoplasm Transplantation
  • Neoplasms, Hormone-Dependent (pathology, prevention & control, secondary)
  • Organ Specificity
  • Osteolysis (etiology, prevention & control)
  • Receptor Activator of Nuclear Factor-kappa B (biosynthesis, genetics)
  • Recombinant Fusion Proteins (physiology)
  • Specific Pathogen-Free Organisms
  • Transduction, Genetic
  • Xenograft Model Antitumor Assays

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