Induction of paclitaxel resistance by ERα mediated prohibitin mitochondrial-nuclear shuttling.

Paclitaxel is a drug within one of the most promising classes of anticancer agents. Unfortunately, clinical success of this drug has been limited by the insurgence of cellular resistance. To address this, Paclitaxel resistance was modeled in an in vitro system using estrogen treated prostate cancer...

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Autores principales:	Pei Dong, Lijuan Jiang, Jianye Liu, Zhiming Wu, Shengjie Guo, Ziling Zhang, Fangjian Zhou, Zhuowei Liu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cac872817d27418e84e1b78a2020dc89
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spelling	oai:doaj.org-article:cac872817d27418e84e1b78a2020dc892021-11-18T08:40:36ZInduction of paclitaxel resistance by ERα mediated prohibitin mitochondrial-nuclear shuttling.1932-620310.1371/journal.pone.0083519https://doaj.org/article/cac872817d27418e84e1b78a2020dc892013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24376711/?tool=EBIhttps://doaj.org/toc/1932-6203Paclitaxel is a drug within one of the most promising classes of anticancer agents. Unfortunately, clinical success of this drug has been limited by the insurgence of cellular resistance. To address this, Paclitaxel resistance was modeled in an in vitro system using estrogen treated prostate cancer cells. This study demonstrates that emerging resistance to clinically relevant doses of Paclitaxel is associated with 17-β-estradiol (E2) treatment in PC-3 cells, but not in LNCaP cells. We found that small interfering RNA mediated knockdown of ERα lead to a decrease in E2 induced Paclitaxel resistance in androgen-independent cells. We also showed that ERα mediated the effects of estrogen, thereby suppressing androgen-independent cell proliferation and mediating Paclitaxel resistance. Furthermore, E2 promoted Prohibitin (PHB) mitochondrial-nucleus translocation via directly mediation of ERα, leading to an inhibition of cellular proliferation by PHB. Additionally, restoration of Paclitaxel sensitivity by ERα knockdown could be overcome by PHB overexpression and, conversely, PHB knockdown decreased E2 induced Paclitaxel resistance. These findings demonstrate that PHB lies downstream of ERα and mediates estrogen-dependent Paclitaxel resistance signaling cascades.Pei DongLijuan JiangJianye LiuZhiming WuShengjie GuoZiling ZhangFangjian ZhouZhuowei LiuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e83519 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pei Dong Lijuan Jiang Jianye Liu Zhiming Wu Shengjie Guo Ziling Zhang Fangjian Zhou Zhuowei Liu Induction of paclitaxel resistance by ERα mediated prohibitin mitochondrial-nuclear shuttling.
description	Paclitaxel is a drug within one of the most promising classes of anticancer agents. Unfortunately, clinical success of this drug has been limited by the insurgence of cellular resistance. To address this, Paclitaxel resistance was modeled in an in vitro system using estrogen treated prostate cancer cells. This study demonstrates that emerging resistance to clinically relevant doses of Paclitaxel is associated with 17-β-estradiol (E2) treatment in PC-3 cells, but not in LNCaP cells. We found that small interfering RNA mediated knockdown of ERα lead to a decrease in E2 induced Paclitaxel resistance in androgen-independent cells. We also showed that ERα mediated the effects of estrogen, thereby suppressing androgen-independent cell proliferation and mediating Paclitaxel resistance. Furthermore, E2 promoted Prohibitin (PHB) mitochondrial-nucleus translocation via directly mediation of ERα, leading to an inhibition of cellular proliferation by PHB. Additionally, restoration of Paclitaxel sensitivity by ERα knockdown could be overcome by PHB overexpression and, conversely, PHB knockdown decreased E2 induced Paclitaxel resistance. These findings demonstrate that PHB lies downstream of ERα and mediates estrogen-dependent Paclitaxel resistance signaling cascades.
format	article
author	Pei Dong Lijuan Jiang Jianye Liu Zhiming Wu Shengjie Guo Ziling Zhang Fangjian Zhou Zhuowei Liu
author_facet	Pei Dong Lijuan Jiang Jianye Liu Zhiming Wu Shengjie Guo Ziling Zhang Fangjian Zhou Zhuowei Liu
author_sort	Pei Dong
title	Induction of paclitaxel resistance by ERα mediated prohibitin mitochondrial-nuclear shuttling.
title_short	Induction of paclitaxel resistance by ERα mediated prohibitin mitochondrial-nuclear shuttling.
title_full	Induction of paclitaxel resistance by ERα mediated prohibitin mitochondrial-nuclear shuttling.
title_fullStr	Induction of paclitaxel resistance by ERα mediated prohibitin mitochondrial-nuclear shuttling.
title_full_unstemmed	Induction of paclitaxel resistance by ERα mediated prohibitin mitochondrial-nuclear shuttling.
title_sort	induction of paclitaxel resistance by erα mediated prohibitin mitochondrial-nuclear shuttling.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/cac872817d27418e84e1b78a2020dc89
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Induction of paclitaxel resistance by ERα mediated prohibitin mitochondrial-nuclear shuttling.

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