Inhibition of Skeletal Metastasis by Ectopic ERα Expression in ERα-Negative Human Breast Cancer Cell Lines

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 hormoneresistant breast cancer progression. In this study, we have investigated the effect of the ectop...

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Main Authors: Abhik Bandyopadhyay, Long Wang, Shiau Hui Chin, Lu-Zhe Sun
Format: Article
Language:English
Published: Elsevier 2007-02-01
Series:Neoplasia: An International Journal for Oncology Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1476558607800418
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author Abhik Bandyopadhyay
Long Wang
Shiau Hui Chin
Lu-Zhe Sun
author_facet Abhik Bandyopadhyay
Long Wang
Shiau Hui Chin
Lu-Zhe Sun
author_sort Abhik Bandyopadhyay
collection DOAJ
description 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 hormoneresistant 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 aVα3 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 ERa-negative human breast cancer cells can inhibit their aggressive bone-metastatic potential in an experimental bone metastasis model.
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spelling doaj.art-54469757504b41d2a8127c5a0d24c2e32022-12-21T18:01:54ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022007-02-019211311810.1593/neo.06784Inhibition of Skeletal Metastasis by Ectopic ERα Expression in ERα-Negative Human Breast Cancer Cell LinesAbhik Bandyopadhyay0Long Wang1Shiau Hui Chin2Lu-Zhe Sun3Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229, USADepartment of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229, USADepartment of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229, USASan Antonio Cancer Institute, University of Texas Health Science Center, San Antonio, TX 78229, USASome 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 hormoneresistant 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 aVα3 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 ERa-negative human breast cancer cells can inhibit their aggressive bone-metastatic potential in an experimental bone metastasis model.http://www.sciencedirect.com/science/article/pii/S1476558607800418Skeletal metastasisestrogen receptorbreast cancerwholemouse imagingmetastasis-related genes
spellingShingle Abhik Bandyopadhyay
Long Wang
Shiau Hui Chin
Lu-Zhe Sun
Inhibition of Skeletal Metastasis by Ectopic ERα Expression in ERα-Negative Human Breast Cancer Cell Lines
Neoplasia: An International Journal for Oncology Research
Skeletal metastasis
estrogen receptor
breast cancer
wholemouse imaging
metastasis-related genes
title Inhibition of Skeletal Metastasis by Ectopic ERα Expression in ERα-Negative Human Breast Cancer Cell Lines
title_full Inhibition of Skeletal Metastasis by Ectopic ERα Expression in ERα-Negative Human Breast Cancer Cell Lines
title_fullStr Inhibition of Skeletal Metastasis by Ectopic ERα Expression in ERα-Negative Human Breast Cancer Cell Lines
title_full_unstemmed Inhibition of Skeletal Metastasis by Ectopic ERα Expression in ERα-Negative Human Breast Cancer Cell Lines
title_short Inhibition of Skeletal Metastasis by Ectopic ERα Expression in ERα-Negative Human Breast Cancer Cell Lines
title_sort inhibition of skeletal metastasis by ectopic erα expression in erα negative human breast cancer cell lines
topic Skeletal metastasis
estrogen receptor
breast cancer
wholemouse imaging
metastasis-related genes
url http://www.sciencedirect.com/science/article/pii/S1476558607800418
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AT shiauhuichin inhibitionofskeletalmetastasisbyectopiceraexpressionineranegativehumanbreastcancercelllines
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