ZNF703 gene amplification at 8p12 specifies luminal B breast cancer.
ZNF703 gene amplification at 8p12 specifies luminal B breast cancer.
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DOI：
10.1002/emmm.201100121
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发表时间：
2011-03
影响因子：
11.1
通讯作者：
Ginestier, Christophe
中科院分区：
文献类型：
--
作者：
Sircoulomb, Fabrice;Nicolas, Nathalie;Ferrari, Anthony;Finetti, Pascal;Bekhouche, Ismahane;Rousselet, Estelle;Lonigro, Aurelie;Adelaide, Jose;Baudelet, Emilie;Esteyries, Severine;Wicinski, Julien;Audebert, Stephane;Charafe-Jauffret, Emmanuelle;Jacquemier, Jocelyne;Lopez, Marc;Borg, Jean-Paul;Sotirious, Christos;Popovici, Cornel;Bertucci, Francois;Birnbaum, Daniel;Chaffanet, Max;Ginestier, Christophe
在包括单独激素治疗在内的所有辅助系统治疗类别中，腔性B型乳腺癌只占雌激素受体(ER)阳性肿瘤的一小部分，与低复发率和疾病特异性存活率有关。识别驱动腔B生物学的特定信号通路对改善治疗至关重要。我们通过对基因组拷贝数、畸变率和基因表达的联合分析，研究了100例腔内乳腺肿瘤。我们发现位于染色体8p12区域的ZNF703基因的扩增优先发生在腔性B肿瘤中。我们通过在MCF7细胞系中过表达ZNF703来探讨ZNF703在B腔肿瘤中的功能作用。我们用质谱仪鉴定了ZNF703是由DCAF7、PHB2和NCOR2组成的核复合体的辅助因子。ZNF703的表达导致干细胞相关基因表达的激活，导致癌症干细胞的增加。此外，我们还发现ZNF703参与了ER和E2F1转录因子的调控。这些发现指出ZNF703在转录调控、干细胞调控和腔B癌发生中的重要作用。
Luminal B breast cancers represent a fraction of oestrogen receptor (ER)-positive tumours associated with poor recurrence-free and disease-specific survival in all adjuvant systemic treatment categories including hormone therapy alone. Identification of specific signalling pathways driving luminal B biology is paramount to improve treatment. We have studied 100 luminal breast tumours by combined analysis of genome copy number aberrations and gene expression. We show that amplification of the ZNF703 gene, located in chromosomal region 8p12, preferentially occurs in luminal B tumours. We explored the functional role of ZNF703 in luminal B tumours by overexpressing ZNF703 in the MCF7 luminal cell line. Using mass spectrometry, we identified ZNF703 as a co-factor of a nuclear complex comprising DCAF7, PHB2 and NCOR2. ZNF703 expression results in the activation of stem cell-related gene expression leading to an increase in cancer stem cells. Moreover, we show that ZNF703 is implicated in the regulation of ER and E2F1 transcription factor. These findings point out the prominent role of ZNF703 in transcription modulation, stem cell regulation and luminal B oncogenesis.
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影响因子：
3
作者：
Chen H;Sharp BM
通讯作者：
Sharp BM
影响因子：
12.3
作者：
Adler P;Kolde R;Kull M;Tkachenko A;Peterson H;Reimand J;Vilo J
通讯作者：
Vilo J
DOI：
10.4161/cc.8.20.9761
发表时间：
2009-10-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Ginestier C;Wicinski J;Cervera N;Monville F;Finetti P;Bertucci F;Wicha MS;Birnbaum D;Charafe-Jauffret E
通讯作者：
Charafe-Jauffret E
影响因子：
5.8
作者：
Benito, M;Parker, J;Marron, JS
通讯作者：
Marron, JS
影响因子：
6.4
作者：
Cariati, Massimiliano;Naderi, Ali;Purushotham, Anand D.
通讯作者：
Purushotham, Anand D.