Identification of primary gene targets of TFAP2C in hormone responsive breast carcinoma cells.
Identification of primary gene targets of TFAP2C in hormone responsive breast carcinoma cells.
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DOI：
10.1002/gcc.20807
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发表时间：
2010-10
影响因子：
3.7
通讯作者：
Weigel, Ronald J.
中科院分区：
文献类型：
--
作者：
Woodfield, George W.;Chen, Yizhen;Bair, Thomas B.;Domann, Frederick E.;Weigel, Ronald J.
TFAP 2C转录因子参与乳腺发育、分化和肿瘤发生。先前的研究确定了TFAP 2C在乳腺癌中调节ESR 1（ERα）和ERBB 2（Her 2）的作用。然而，TFAP 2C在不同乳腺癌表型中的作用尚未详细研究。为了开发TFAP 2C靶基因的更完整表征，在MCF-7乳腺癌细胞中分析了具有抗TFAP 2C抗体的ChIP-seq和具有TFAP 2C敲低的表达阵列。ChIP-seq数据集共有的基因组序列将TFAP 2C染色质结合的共有序列定义为9个碱基序列SCCTSRGGS（S=G/C，R=A/G），其与先前定义的最佳体外结合位点密切匹配。将TFAP 2C敲低前后的表达阵列与ChIP-seq数据进行比较，证明保守估计8%被TFAP 2C表达改变的基因是主要靶基因，包括被TFAP 2C诱导和抑制的基因。TFAP 2C的主要靶基因包括ESR 1（ERα）、FREM 2、RET、FOXA 1、WWOX、GREB 1、MYC和维甲酸反应通路成员，共447个。ESR 1、WWOX、GREB 1和FOXA 1作为主要靶点的鉴定证实了TFAP 2C在激素应答中的作用。TFAP 2C在激素应答性乳腺癌的基因调控中起关键作用，其靶基因与Her 2乳腺癌表型不同。
The TFAP2C transcription factor is involved in mammary development, differentiation and oncogenesis. Previous studies established a role for TFAP2C in the regulation of ESR1 (ERα) 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 (ERα), 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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影响因子：
46.9
作者：
Ji, Hongkai;Jiang, Hui;Ma, Wenxiu;Johnson, David S.;Myers, Richard M.;Wong, Wing H.
通讯作者：
Wong, Wing H.
影响因子：
6.4
作者：
Friedrichs, N.;Steiner, S.;Knoepfle, G.
通讯作者：
Knoepfle, G.
影响因子：
4.8
作者：
Begon, DY;Delacroix, L;Winkler, R
通讯作者：
Winkler, R
DOI：
10.1186/bcr1851
发表时间：
2008
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Allouche A;Nolens G;Tancredi A;Delacroix L;Mardaga J;Fridman V;Winkler R;Boniver J;Delvenne P;Begon DY
通讯作者：
Begon DY
DOI：
10.1002/jez.b.21189
发表时间：
2007-09-15
影响因子：
2.2
作者：
Hoffman, Trevor L.;Javier, Anna L.;Schilling, Thomas F.
通讯作者：
Schilling, Thomas F.