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.
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Authors | George W Woodfield, Yizhen Chen, Thomas B Bair, Frederick E Domann, Ronald J Weigel |
Journal | Genes, chromosomes & cancer
(Genes Chromosomes Cancer)
Vol. 49
Issue 10
Pg. 948-62
(Oct 2010)
ISSN: 1098-2264 [Electronic] United States |
PMID | 20629094
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers, Tumor
- RNA, Messenger
- RNA, Small Interfering
- TFAP2C protein, human
- Transcription Factor AP-2
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Topics |
- Biomarkers, Tumor
(genetics, metabolism)
- Breast Neoplasms
(genetics, metabolism, pathology)
- Cell Line, Tumor
- Chromatin Immunoprecipitation
- Female
- Gene Expression Profiling
- Gene Expression Regulation, Neoplastic
- Humans
- Neoplasms, Hormone-Dependent
(genetics, metabolism, pathology)
- Oligonucleotide Array Sequence Analysis
- Promoter Regions, Genetic
(genetics)
- RNA, Messenger
(genetics)
- RNA, Small Interfering
(pharmacology)
- Reverse Transcriptase Polymerase Chain Reaction
- Transcription Factor AP-2
(antagonists & inhibitors, genetics, metabolism)
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