Identification of primary gene targets of TFAP2C in hormone responsive breast carcinoma cells

George W Woodfield; Yizhen Chen; Thomas B Bair; Frederick E Domann; Ronald J Weigel

doi:10.1002/gcc.20807

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Identification of primary gene targets of TFAP2C in hormone responsive breast carcinoma cells

Journal article

Peer reviewed

Identification of primary gene targets of TFAP2C in hormone responsive breast carcinoma cells

George W Woodfield, Yizhen Chen, Thomas B Bair, Frederick E Domann and Ronald J Weigel

Genes chromosomes & cancer, Vol.49(10), pp.948-962

10/2010

DOI: 10.1002/gcc.20807

PMCID: PMC2928401

PMID: 20629094

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Abstract

The TFAP2C transcription factor is involved in mammary development, differentiation, and oncogenesis. Previous studies established a role for TFAP2C in the regulation of ESR1 (ERalpha) and ERBB2 (Her2) in breast carcinomas. However, the role of TFAP2C in different breast cancer phenotypes has not been examined in detail. To develop a more complete characterization of TFAP2C target genes, ChIP-seq with anti-TFAP2C antibody and expression arrays with TFAP2C knock down were analyzed in MCF-7 breast carcinoma cells. Genomic sequences common to the ChIP-seq data set defined the consensus sequence for TFAP2C chromatin binding as the nine base sequence SCCTSRGGS (S = G/C, r = A/G), which closely matches the previously defined optimal in vitro binding site. Comparing expression arrays before and after knock down of TFAP2C with ChIP-seq data demonstrated a conservative estimate that 8% of genes altered by TFAP2C expression are primary target genes and includes genes that are both induced and repressed by TFAP2C. A set of 447 primary target genes of TFAP2C was identified, which included ESR1 (ERalpha), FREM2, RET, FOXA1, WWOX, GREB1, MYC, and members of the retinoic acid response pathway. The identification of ESR1, WWOX, GREB1, and FOXA1 as primary targets confirmed the role of TFAP2C in hormone response. TFAP2C plays a critical role in gene regulation in hormone responsive breast cancer and its target genes are different than for the Her2 breast cancer phenotype.

Neoplasms, Hormone-Dependent - metabolism

Transcription Factor AP-2 - antagonists & inhibitors

Oligonucleotide Array Sequence Analysis

Humans

RNA, Messenger - genetics

RNA, Small Interfering - pharmacology

Gene Expression Regulation, Neoplastic

Gene Expression Profiling

Reverse Transcriptase Polymerase Chain Reaction

Promoter Regions, Genetic - genetics

Transcription Factor AP-2 - metabolism

Breast Neoplasms - metabolism

Neoplasms, Hormone-Dependent - genetics

Transcription Factor AP-2 - genetics

Breast Neoplasms - genetics

Chromatin Immunoprecipitation

Breast Neoplasms - pathology

Neoplasms, Hormone-Dependent - pathology

Biomarkers, Tumor - metabolism

Cell Line, Tumor

Female

Biomarkers, Tumor - genetics

Details

Title: Subtitle: Identification of primary gene targets of TFAP2C in hormone responsive breast carcinoma cells
Creators: George W Woodfield - Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
Yizhen Chen
Thomas B Bair
Frederick E Domann
Ronald J Weigel
Resource Type: Journal article
Publication Details: Genes chromosomes & cancer, Vol.49(10), pp.948-962
DOI: 10.1002/gcc.20807
PMID: 20629094
PMCID: PMC2928401
NLM abbreviation: Genes Chromosomes Cancer
ISSN: 1045-2257
eISSN: 1098-2264
Publisher: United States
Grant note: R01CA109294 / NCI NIH HHS R01 CA109294 / NCI NIH HHS
Language: English
Date published: 10/2010
Academic Unit: Molecular Physiology and Biophysics; Anatomy and Cell Biology; Pathology; Surgery; Radiation Oncology; Biochemistry and Molecular Biology
Record Identifier: 9984025287802771

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