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Open Access Highly Accessed Research article

An integrative analysis of cellular contexts, miRNAs and mRNAs reveals network clusters associated with antiestrogen-resistant breast cancer cells

Seungyoon Nam12*, Xinghua Long23, ChangHyuk Kwon1, Sun Kim4 and Kenneth P Nephew2

Author Affiliations

1 Cancer Genomics Branch, National Cancer Center, Goyang-si, Gyeonggi-do, 410-769, Korea

2 Department of Cellular and Integrative Physiology, Medical Sciences Program, Indiana University School of Medicine, Bloomington, IN 47405, USA

3 Zhongnan Hospital, Wuhan University, Wuhan, 430071, China

4 Department of Computer Science and Engineering, Bioinformatics Institute, Seoul National University, Seoul, 151-742, Korea

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BMC Genomics 2012, 13:732  doi:10.1186/1471-2164-13-732

Published: 27 December 2012

Additional files

Additional file 1:

Study overview. Integrative network with miRNAs, mRNAs, expressions, and cancer-related contexts in acquired resistance to antiestrogen in breast cancer cells (tamoxifen resistant (MCF7-T), fulvestrant resistant (MCF7-F), and parental drug-sensitive MCF7 cells). For minimizing false positives in network connectivity, we used experimentally validated databases: TransmiR (TFs binding in miRNA promoters, signaling proteins for regulating miRNAs), and miRTarBase (miRNA target information). In addition, biological interpretability was enhanced by incorporating cancer-related context terms suggested by Hanahan and Weinberg [24] into the network connectivity. The cancer contexts were connected with TFs, signaling proteins, and miRNA targets from the two databases by using a text-mining tool, PubGene [26]. The antiestrogen resistant cell line expressions were incorporated into the network connectivity (see the details in the Methods section), and the network clusters underscoring the antiestrogen resistances were identified by the Cytoscape clusterMaker [29].

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Additional file 2:

Statistical validation of the regulations in the network. The detailed information is described in this material.

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Additional file 3:

Genes involved in molecular mechanisms of DNA damage response via BRCA1 and BRCA2. The genes listed refer to Roy et al. [34].

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Additional file 4:

Fold-change of mRNAs. The fold changes of MCF7-T over MCF7 and MCF7-F over MCF7 were summarized from our previous study [2]. The positive fold change means that the drug-resistant cell line is greater than MCF7, and the negative fold change vice versa.

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Additional file 5:

The processed expression of miRNA microarrays. The expression values were log2-transformed.

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