Disruption of the ER-α36-EGFR/HER2 positive regulatory loops restores tamoxifen sensitivity in tamoxifen resistance breast cancer cells.

Tamoxifen provided a successful treatment for ER-positive breast cancer for many years. However, most breast tumors develop tamoxifen resistance and are eventually refractory to tamoxifen therapy. The molecular mechanisms underlying development of tamoxifen resistance have not been well established....

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Li Yin, Xin-Tian Zhang, Xiu-Wu Bian, Yu-Ming Guo, Zhao-Yi Wang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e75f295411d643b0b0d0a8e177b7c565
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e75f295411d643b0b0d0a8e177b7c565
record_format	dspace
spelling	oai:doaj.org-article:e75f295411d643b0b0d0a8e177b7c5652021-11-25T06:01:21ZDisruption of the ER-α36-EGFR/HER2 positive regulatory loops restores tamoxifen sensitivity in tamoxifen resistance breast cancer cells.1932-620310.1371/journal.pone.0107369https://doaj.org/article/e75f295411d643b0b0d0a8e177b7c5652014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0107369https://doaj.org/toc/1932-6203Tamoxifen provided a successful treatment for ER-positive breast cancer for many years. However, most breast tumors develop tamoxifen resistance and are eventually refractory to tamoxifen therapy. The molecular mechanisms underlying development of tamoxifen resistance have not been well established. Recently, we reported that breast cancer cells with high levels of ER-α36, a variant of ER-α, were resistant to tamoxifen and knockdown of ER-α36 expression in tamoxifen resistant cells with the shRNA method restored tamoxifen sensitivity, indicating that gained ER-α36 expression is one of the underlying mechanisms of tamoxifen resistance. Here, we found that tamoxifen induced expression of ER-α36-EGFR/HER2 positive regulatory loops and tamoxifen resistant MCF7 cells (MCF7/TAM) expressed enhanced levels of the loops. Disruption of the ER-α36-EGFR/HER2 positive regulatory loops with the dual tyrosine kinase inhibitor Lapatinib or ER-α36 down-regulator Broussoflavonol B in tamoxifen resistant MCF7 cells restored tamoxifen sensitivity. In addition, we also found both Lapatinib and Broussoflavonol B increased the growth inhibitory activity of tamoxifen in tumorsphere cells derived from MCF7/TAM cells. Our results thus demonstrated that elevated expression of the ER-α36-EGFR/HER2 loops is one of the mechanisms by which ER-positive breast cancer cells escape tamoxifen therapy. Our results thus provided a rational to develop novel therapeutic approaches for tamoxifen resistant patients by targeting the ER-α36-EGFR/HER2 loops.Li YinXin-Tian ZhangXiu-Wu BianYu-Ming GuoZhao-Yi WangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e107369 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Li Yin Xin-Tian Zhang Xiu-Wu Bian Yu-Ming Guo Zhao-Yi Wang Disruption of the ER-α36-EGFR/HER2 positive regulatory loops restores tamoxifen sensitivity in tamoxifen resistance breast cancer cells.
description	Tamoxifen provided a successful treatment for ER-positive breast cancer for many years. However, most breast tumors develop tamoxifen resistance and are eventually refractory to tamoxifen therapy. The molecular mechanisms underlying development of tamoxifen resistance have not been well established. Recently, we reported that breast cancer cells with high levels of ER-α36, a variant of ER-α, were resistant to tamoxifen and knockdown of ER-α36 expression in tamoxifen resistant cells with the shRNA method restored tamoxifen sensitivity, indicating that gained ER-α36 expression is one of the underlying mechanisms of tamoxifen resistance. Here, we found that tamoxifen induced expression of ER-α36-EGFR/HER2 positive regulatory loops and tamoxifen resistant MCF7 cells (MCF7/TAM) expressed enhanced levels of the loops. Disruption of the ER-α36-EGFR/HER2 positive regulatory loops with the dual tyrosine kinase inhibitor Lapatinib or ER-α36 down-regulator Broussoflavonol B in tamoxifen resistant MCF7 cells restored tamoxifen sensitivity. In addition, we also found both Lapatinib and Broussoflavonol B increased the growth inhibitory activity of tamoxifen in tumorsphere cells derived from MCF7/TAM cells. Our results thus demonstrated that elevated expression of the ER-α36-EGFR/HER2 loops is one of the mechanisms by which ER-positive breast cancer cells escape tamoxifen therapy. Our results thus provided a rational to develop novel therapeutic approaches for tamoxifen resistant patients by targeting the ER-α36-EGFR/HER2 loops.
format	article
author	Li Yin Xin-Tian Zhang Xiu-Wu Bian Yu-Ming Guo Zhao-Yi Wang
author_facet	Li Yin Xin-Tian Zhang Xiu-Wu Bian Yu-Ming Guo Zhao-Yi Wang
author_sort	Li Yin
title	Disruption of the ER-α36-EGFR/HER2 positive regulatory loops restores tamoxifen sensitivity in tamoxifen resistance breast cancer cells.
title_short	Disruption of the ER-α36-EGFR/HER2 positive regulatory loops restores tamoxifen sensitivity in tamoxifen resistance breast cancer cells.
title_full	Disruption of the ER-α36-EGFR/HER2 positive regulatory loops restores tamoxifen sensitivity in tamoxifen resistance breast cancer cells.
title_fullStr	Disruption of the ER-α36-EGFR/HER2 positive regulatory loops restores tamoxifen sensitivity in tamoxifen resistance breast cancer cells.
title_full_unstemmed	Disruption of the ER-α36-EGFR/HER2 positive regulatory loops restores tamoxifen sensitivity in tamoxifen resistance breast cancer cells.
title_sort	disruption of the er-α36-egfr/her2 positive regulatory loops restores tamoxifen sensitivity in tamoxifen resistance breast cancer cells.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/e75f295411d643b0b0d0a8e177b7c565
work_keys_str_mv	AT liyin disruptionoftheera36egfrher2positiveregulatoryloopsrestorestamoxifensensitivityintamoxifenresistancebreastcancercells AT xintianzhang disruptionoftheera36egfrher2positiveregulatoryloopsrestorestamoxifensensitivityintamoxifenresistancebreastcancercells AT xiuwubian disruptionoftheera36egfrher2positiveregulatoryloopsrestorestamoxifensensitivityintamoxifenresistancebreastcancercells AT yumingguo disruptionoftheera36egfrher2positiveregulatoryloopsrestorestamoxifensensitivityintamoxifenresistancebreastcancercells AT zhaoyiwang disruptionoftheera36egfrher2positiveregulatoryloopsrestorestamoxifensensitivityintamoxifenresistancebreastcancercells
_version_	1718414312725282816

Disruption of the ER-α36-EGFR/HER2 positive regulatory loops restores tamoxifen sensitivity in tamoxifen resistance breast cancer cells.

Ejemplares similares