Genome-wide mapping of FOXM1 binding reveals co-binding with estrogen receptor alpha in breast cancer cells.
Genome-wide mapping of FOXM1 binding reveals co-binding with estrogen receptor alpha in breast cancer cells.
复制标题
DOI：
10.1186/gb-2013-14-1-r6
复制
发表时间：
2013-01-24
期刊：
影响因子：
12.3
通讯作者：
Balasubramanian S
中科院分区：
文献类型：
--
作者：
Sanders DA;Ross-Innes CS;Beraldi D;Carroll JS;Balasubramanian S
叉头转录因子FOXM1是细胞周期的关键调节因子。它经常在癌症中过度表达，并正在成为一个重要的治疗靶点。在乳腺癌中，FOXM1表达与雌激素受体（ERα）活性和对内分泌治疗的抵抗有关，高水平与预后不良相关。然而，FOXM1在ER阳性乳腺癌中的确切作用尚未完全了解。该研究利用染色质免疫沉淀，然后进行高通量测序，以绘制ERα阳性和阴性乳腺癌细胞系中的FOXM1结合图谱。两种细胞系中结合位点分布的比较揭示了FOXM 1与ERα结合之间先前未描述的关系。进一步的分子生物学分析表明，这两种因子可以同时结合在基因组位点上，FOXM1通过与辅激活因子CARM1相互作用调节ERα的转录活性。使用天然产物硫链丝菌素抑制FOXM1活性揭示了一组FOXM1调节基因的下调，这些基因与临床乳腺癌样本中的患者结果相关。这些发现揭示了FOXM1在乳腺癌ERα转录活性中的新作用，并揭示了FOXM1调节的与ER阳性乳腺癌患者预后相关的基因特征。
The forkhead transcription factor FOXM1 is a key regulator of the cell cycle. It is frequently over-expressed in cancer and is emerging as an important therapeutic target. In breast cancer FOXM1 expression is linked with estrogen receptor (ERα) activity and resistance to endocrine therapies, with high levels correlated with poor prognosis. However, the precise role of FOXM1 in ER positive breast cancer is not yet fully understood. The study utilizes chromatin immunoprecipitation followed by high-throughput sequencing to map FOXM1 binding in both ERα-positive and -negative breast cancer cell lines. The comparison between binding site distributions in the two cell lines uncovered a previously undescribed relationship between binding of FOXM1 and ERα. Further molecular analyses demonstrated that these two factors can bind simultaneously at genomic sites and furthermore that FOXM1 regulates the transcriptional activity of ERα via interaction with the coactivator CARM1. Inhibition of FOXM1 activity using the natural product thiostrepton revealed down-regulation of a set of FOXM1-regulated genes that are correlated with patient outcome in clinical breast cancer samples. These findings reveal a novel role for FOXM1 in ERα transcriptional activity in breast cancer and uncover a FOXM1-regulated gene signature associated with ER-positive breast cancer patient prognosis.
登录
查看更多内容
影响因子：
3.8
作者：
Bektas, Nuran;ten Haaf, Anette;Veeck, Juergen;Wild, Peter Johannes;Luescher-Firzlaff, Juliane;Hartmann, Arndt;Knuechel, Ruth;Dahl, Edgar
通讯作者：
Dahl, Edgar
影响因子：
50.3
作者：
Anders L;Ke N;Hydbring P;Choi YJ;Widlund HR;Chick JM;Zhai H;Vidal M;Gygi SP;Braun P;Sicinski P
通讯作者：
Sicinski P
影响因子：
10.5
作者：
Ceschin, Danilo Guillermo;Walia, Mannu;Gronemeyer, Hinrich
通讯作者：
Gronemeyer, Hinrich
影响因子：
5.2
作者：
Francis RE;Myatt SS;Krol J;Hartman J;Peck B;McGovern UB;Wang J;Guest SK;Filipovic A;Gojis O;Palmieri C;Peston D;Shousha S;Yu Q;Sicinski P;Coombes RC;Lam EW
通讯作者：
Lam EW
影响因子：
8.8
作者：
Gozgit, J. M.;Pentecost, B. T.;Marconi, S. A.;Ricketts-Loriaux, R. S. J.;Otis, C. N.;Arcaro, K. F.
通讯作者：
Arcaro, K. F.