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Differential Gene Expression in Tamoxifen-Resistant Breast Cancer Cells Revealed by a New Analytical Model of RNA-Seq Data

Resistance to tamoxifen (Tam), a widely used antagonist of the estrogen receptor (ER), is a common obstacle to successful breast cancer treatment. While adjuvant therapy with Tam has been shown to significantly decrease the rate of disease recurrence and mortality, recurrent disease occurs in one th...

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Autores principales: Huber-Keener, Kathryn J., Liu, Xiuping, Wang, Zhong, Wang, Yaqun, Freeman, Willard, Wu, Song, Planas-Silva, Maricarmen D., Ren, Xingcong, Cheng, Yan, Zhang, Yi, Vrana, Kent, Liu, Chang-Gong, Yang, Jin-Ming, Wu, Rongling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402532/
https://www.ncbi.nlm.nih.gov/pubmed/22844461
http://dx.doi.org/10.1371/journal.pone.0041333
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author Huber-Keener, Kathryn J.
Liu, Xiuping
Wang, Zhong
Wang, Yaqun
Freeman, Willard
Wu, Song
Planas-Silva, Maricarmen D.
Ren, Xingcong
Cheng, Yan
Zhang, Yi
Vrana, Kent
Liu, Chang-Gong
Yang, Jin-Ming
Wu, Rongling
author_facet Huber-Keener, Kathryn J.
Liu, Xiuping
Wang, Zhong
Wang, Yaqun
Freeman, Willard
Wu, Song
Planas-Silva, Maricarmen D.
Ren, Xingcong
Cheng, Yan
Zhang, Yi
Vrana, Kent
Liu, Chang-Gong
Yang, Jin-Ming
Wu, Rongling
author_sort Huber-Keener, Kathryn J.
collection PubMed
description Resistance to tamoxifen (Tam), a widely used antagonist of the estrogen receptor (ER), is a common obstacle to successful breast cancer treatment. While adjuvant therapy with Tam has been shown to significantly decrease the rate of disease recurrence and mortality, recurrent disease occurs in one third of patients treated with Tam within 5 years of therapy. A better understanding of gene expression alterations associated with Tam resistance will facilitate circumventing this problem. Using a next generation sequencing approach and a new bioinformatics model, we compared the transcriptomes of Tam-sensitive and Tam-resistant breast cancer cells for identification of genes involved in the development of Tam resistance. We identified differential expression of 1215 mRNA and 513 small RNA transcripts clustered into ERα functions, cell cycle regulation, transcription/translation, and mitochondrial dysfunction. The extent of alterations found at multiple levels of gene regulation highlights the ability of the Tam-resistant cells to modulate global gene expression. Alterations of small nucleolar RNA, oxidative phosphorylation, and proliferation processes in Tam-resistant cells present areas for diagnostic and therapeutic tool development for combating resistance to this anti-estrogen agent.
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spelling pubmed-34025322012-07-27 Differential Gene Expression in Tamoxifen-Resistant Breast Cancer Cells Revealed by a New Analytical Model of RNA-Seq Data Huber-Keener, Kathryn J. Liu, Xiuping Wang, Zhong Wang, Yaqun Freeman, Willard Wu, Song Planas-Silva, Maricarmen D. Ren, Xingcong Cheng, Yan Zhang, Yi Vrana, Kent Liu, Chang-Gong Yang, Jin-Ming Wu, Rongling PLoS One Research Article Resistance to tamoxifen (Tam), a widely used antagonist of the estrogen receptor (ER), is a common obstacle to successful breast cancer treatment. While adjuvant therapy with Tam has been shown to significantly decrease the rate of disease recurrence and mortality, recurrent disease occurs in one third of patients treated with Tam within 5 years of therapy. A better understanding of gene expression alterations associated with Tam resistance will facilitate circumventing this problem. Using a next generation sequencing approach and a new bioinformatics model, we compared the transcriptomes of Tam-sensitive and Tam-resistant breast cancer cells for identification of genes involved in the development of Tam resistance. We identified differential expression of 1215 mRNA and 513 small RNA transcripts clustered into ERα functions, cell cycle regulation, transcription/translation, and mitochondrial dysfunction. The extent of alterations found at multiple levels of gene regulation highlights the ability of the Tam-resistant cells to modulate global gene expression. Alterations of small nucleolar RNA, oxidative phosphorylation, and proliferation processes in Tam-resistant cells present areas for diagnostic and therapeutic tool development for combating resistance to this anti-estrogen agent. Public Library of Science 2012-07-23 /pmc/articles/PMC3402532/ /pubmed/22844461 http://dx.doi.org/10.1371/journal.pone.0041333 Text en Huber-Keener et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Huber-Keener, Kathryn J.
Liu, Xiuping
Wang, Zhong
Wang, Yaqun
Freeman, Willard
Wu, Song
Planas-Silva, Maricarmen D.
Ren, Xingcong
Cheng, Yan
Zhang, Yi
Vrana, Kent
Liu, Chang-Gong
Yang, Jin-Ming
Wu, Rongling
Differential Gene Expression in Tamoxifen-Resistant Breast Cancer Cells Revealed by a New Analytical Model of RNA-Seq Data
title Differential Gene Expression in Tamoxifen-Resistant Breast Cancer Cells Revealed by a New Analytical Model of RNA-Seq Data
title_full Differential Gene Expression in Tamoxifen-Resistant Breast Cancer Cells Revealed by a New Analytical Model of RNA-Seq Data
title_fullStr Differential Gene Expression in Tamoxifen-Resistant Breast Cancer Cells Revealed by a New Analytical Model of RNA-Seq Data
title_full_unstemmed Differential Gene Expression in Tamoxifen-Resistant Breast Cancer Cells Revealed by a New Analytical Model of RNA-Seq Data
title_short Differential Gene Expression in Tamoxifen-Resistant Breast Cancer Cells Revealed by a New Analytical Model of RNA-Seq Data
title_sort differential gene expression in tamoxifen-resistant breast cancer cells revealed by a new analytical model of rna-seq data
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402532/
https://www.ncbi.nlm.nih.gov/pubmed/22844461
http://dx.doi.org/10.1371/journal.pone.0041333
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