Paper Info
Title
A modulated empirical Bayes model for identifying topological and temporal estrogen receptor α regulatory networks in breast cancer.
Abstract
Estrogens regulate diverse physiological processes in various tissues through genomic and non-genomic mechanisms that result in activation or repression of gene expression. Transcription regulation upon estrogen stimulation is a critical biological process underlying the onset and progress of the majority of breast cancer. Dynamic gene expression changes have been shown to characterize the breast cancer cell response to estrogens, the every molecular mechanism of which is still not well understood.We developed a modulated empirical Bayes model, and constructed a novel topological and temporal transcription factor (TF) regulatory network in MCF7 breast cancer cell line upon stimulation by 17β-estradiol stimulation. In the network, significant TF genomic hubs were identified including ER-alpha and AP-1; significant non-genomic hubs include ZFP161, TFDP1, NRF1, TFAP2A, EGR1, E2F1, and PITX2. Although the early and late networks were distinct (<5% overlap of ERα target genes between the 4 and 24 h time points), all nine hubs were significantly represented in both networks. In MCF7 cells with acquired resistance to tamoxifen, the ERα regulatory network was unresponsive to 17β-estradiol stimulation. The significant loss of hormone responsiveness was associated with marked epigenomic changes, including hyper- or hypo-methylation of promoter CpG islands and repressive histone methylations.We identified a number of estrogen regulated target genes and established estrogen-regulated network that distinguishes the genomic and non-genomic actions of estrogen receptor. Many gene targets of this network were not active anymore in anti-estrogen resistant cell lines, possibly because their DNA methylation and histone acetylation patterns have changed.
Year
DOI
Venue
2011
10.1186/1752-0509-5-67
BMC systems biology
Keywords
Field
DocType
gene expression,transcription factor,biology,systems biology,gene targeting,breast cancer,cell line,estrogen receptor,algorithms,systems,dna methylation,biological process,transcription regulation,molecular mechanics,bioinformatics,cpg island,histone methylation
Transcriptional regulation,Estrogen,Breast cancer,Biology,Estrogen receptor alpha,Tamoxifen,Bioinformatics,Gene regulatory network,Estrogen receptor,Selective estrogen receptor modulator
Journal
Volume
Issue
ISSN
5
1
1752-0509
Citations 
PageRank 
References 
10
0.50
6
Authors
14
Name
Order
Citations
PageRank
Changyu Shen112512.98
Yiwen Huang2213.63
Yunlong Liu326721.81
Guohua Wang423517.66
Yuming Zhao5100.50
Zhiping Wang61025.30
Mingxiang Teng720513.62
Yadong Wang875480.12
David A Flockhart9482.45
Todd C Skaar10110.90
Pearlly Yan11824.28
K Nephew12768.84
Tim Huang13413.46
Lang Li1411217.66