A Comprehensive Nuclear Receptor Network for Breast Cancer Cells

Ralf Kittler, Jie Zhou, Sujun Hua, Lijia Ma, Yuwen Liu, Elisha Pendleton, Chao Cheng, Mark Gerstein, Kevin P. White

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

In breast cancer, nuclear receptors (NRs) play a prominent role in governing gene expression, have prognostic utility, and are therapeutic targets. We built a regulatory map for 24 NRs, six chromatin state markers, and 14 breast-cancer-associated transcription factors (TFs) that are expressed in the breast cancer cell line MCF-7. The resulting network reveals a highly interconnected regulatory matrix where extensive crosstalk occurs among NRs and other breast -cancer-associated TFs. We show that large numbers of factors are coordinately bound to highly occupied target regions throughout the genome, and these regions are associated with active chromatin state and hormone-responsive gene expression. This network also provides a framework for stratifying and predicting patient outcomes, and we use it to show that the peroxisome proliferator-activated receptor delta binds to a set of genes also regulated by the retinoic acid receptors and whose expression is associated with poor prognosis in breast cancer.

Original languageEnglish (US)
Pages (from-to)538-551
Number of pages14
JournalCell Reports
Volume3
Issue number2
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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