Differential gene expression in tamoxifen-resistant breast cancer cells revealed by a new analytical model of RNA-Seq data

Kathryn J Huber-Keener; Xiuping Liu; Zhong Wang; Yaqun Wang; Willard Freeman; Song Wu; Maricarmen D Planas-Silva; Xingcong Ren; Yan Cheng; Yi Zhang; Kent Vrana; Chang-Gong Liu; Jin-Ming Yang; Rongling Wu

doi:10.1371/journal.pone.0041333

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Differential gene expression in tamoxifen-resistant breast cancer cells revealed by a new analytical model of RNA-Seq data

Journal article

Open access

Peer reviewed

Differential gene expression in tamoxifen-resistant breast cancer cells revealed by a new analytical model of RNA-Seq data

Kathryn J Huber-Keener, Xiuping Liu, Zhong Wang, Yaqun Wang, Willard Freeman, Song Wu, Maricarmen D Planas-Silva, Xingcong Ren, Yan Cheng, Yi Zhang, …

PloS one, Vol.7(7), pp.e41333-e41333

2012

DOI: 10.1371/journal.pone.0041333

PMCID: PMC3402532

PMID: 22844461

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Abstract

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.

Phenotype

Computational Biology - methods

Reproducibility of Results

Humans

RNA, Messenger - genetics

Transcriptome - drug effects

RNA, Messenger - metabolism

RNA, Untranslated - genetics

Drug Resistance, Neoplasm - genetics

Sequence Analysis, RNA

MCF-7 Cells

Breast Neoplasms - pathology

Tamoxifen - pharmacology

High-Throughput Nucleotide Sequencing

Chemotherapy, Adjuvant

Cluster Analysis

Details

Title: Subtitle: Differential gene expression in tamoxifen-resistant breast cancer cells revealed by a new analytical model of RNA-Seq data
Creators: Kathryn J Huber-Keener - Department of Pharmacology, The Penn State Cancer Institute, The Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, Pennsylvania, United States of America
Xiuping Liu
Zhong Wang
Yaqun Wang
Willard Freeman
Song Wu
Maricarmen D Planas-Silva
Xingcong Ren
Yan Cheng
Yi Zhang - Penn State Milton S. Hershey Medical Center
Kent Vrana
Chang-Gong Liu
Jin-Ming Yang
Rongling Wu
Resource Type: Journal article
Publication Details: PloS one, Vol.7(7), pp.e41333-e41333
DOI: 10.1371/journal.pone.0041333
PMID: 22844461
PMCID: PMC3402532
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: United States
Language: English
Date published: 2012
Academic Unit: Obstetrics and Gynecology
Record Identifier: 9983930387302771

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