Identification of gene regulation patterns underlying both oestrogen- and tamoxifen-stimulated cell growth through global gene expression profiling in breast cancer cells.
Identification of gene regulation patterns underlying both oestrogen- and tamoxifen-stimulated cell growth through global gene expression profiling in breast cancer cells.
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DOI：
10.1016/j.ejca.2014.08.010
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发表时间：
2014-11
影响因子：
8.4
通讯作者：
Jordan, V. Craig
中科院分区：
文献类型：
--
作者：
Fan, Ping;Cunliffe, Heather E.;Griffith, Obi L.;Agboke, Fadeke A.;Ramos, Pilar;Gray, Joe W.;Jordan, V. Craig
c-Src抑制剂阻断雌激素（E2）诱导的应激，并将E2反应从诱导凋亡转化为刺激E2缺失的乳腺癌细胞生长。一个重编程的细胞系，MCF-7:PF，产生一个功能性雌激素受体（ER）。我们解决了选择性内质网调节剂4-羟他莫昔芬（4-OHT）是否可以靶向内质网来阻止e2刺激的MCF-7:PF细胞生长的问题。实时RT-PCR检测mRNA表达。通过芯片分析全局基因表达谱。通过rna测序筛选转录组谱。出乎意料的是，4-OHT和E2都以浓度依赖性的方式刺激细胞生长。表达谱显示E2和4-OHT在同一方向上调控的基因显著重叠。对MCF-7:PF细胞中280个常被4-OHT和E2调控的基因进行通路富集分析，发现其功能主要与膜、细胞质和代谢过程有关。进一步分析了98个被4-OHT和E2上调的基因，发现与膜重塑、细胞骨架重组、细胞质适配器蛋白、细胞质细胞器蛋白和相关过程相关的基因显著富集。4-OHT对EHD2、FHL2、HOMER3、RHOF等膜重构分子的上调作用强于E2。相反，在野生型MCF-7细胞中，4-OHT作为拮抗剂抑制了大多数富集膜相关基因的表达。长期的选择压力改变了细胞群对4-OHT的反应。膜相关信号传导是4- oht刺激MCF-7:PF细胞生长的关键。本研究为进一步研究他莫昔芬耐药患者的靶向治疗提供了理论依据。
A c-Src inhibitor blocks estrogen (E2)-induced stress and converts E2 responses from inducing apoptosis to growth stimulation in E2-deprived breast cancer cells. A reprogrammed cell line, MCF-7:PF, results in a functional estrogen receptor (ER). We addressed the question of whether the selective ER modulator 4-hydroxytamoxifen (4-OHT) could target ER to prevent E2-stimulated growth in MCF-7:PF cells. Expression of mRNA was measured through real-time RT-PCR. Global gene expression profile was analyzed through microarray. Transcriptome profiles were screened by RNA-sequencing. Unexpectedly, both 4-OHT and E2 stimulated cell growth in a concentration-dependent manner. Expression profiling showed a remarkable overlap in genes regulated in the same direction by E2 and 4-OHT. Pathway enrichment analysis of the 280 genes commonly deregulated in MCF-7:PF cells by 4-OHT and E2 revealed functions mainly related to membrane, cytoplasm, and metabolic processes. Further analysis of 98 genes up-regulated by both 4-OHT and E2 uncovered a significant enrichment in genes associated with membrane remodeling, cytoskeleton reorganization, cytoplasmic adapter proteins, cytoplasm organelles proteins, and related processes. 4-OHT was more potent than E2 in up-regulating some membrane remodeling molecules, such as EHD2, FHL2, HOMER3 and RHOF. In contrast, 4-OHT acted as an antagonist to inhibit expression of the majority of enriched membrane-associated genes in wild-type MCF-7 cells. Long-term selection pressure has changed the cell population responses to 4-OHT. Membrane-associated signaling is critical for 4-OHT-stimulated cell growth in MCF-7:PF cells. This study provides a rationale for the further investigation of target therapy for tamoxifen resistant patients.
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共轭性雌激素和乳腺癌的发病率和乳腺癌的死亡率以及子宫切除术后妇女：妇女健康计划的扩展随访随机性安慰剂对照试验。
DOI：
10.1016/s1470-2045(12)70075-x
发表时间：
2012-05
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Anderson GL;Chlebowski RT;Aragaki AK;Kuller LH;Manson JE;Gass M;Bluhm E;Connelly S;Hubbell FA;Lane D;Martin L;Ockene J;Rohan T;Schenken R;Wactawski-Wende J
通讯作者：
Wactawski-Wende J
影响因子：
168.9
作者：
Davies, Christina;Pan, Hongchao;Godwin, Jon;Gray, Richard;Arriagada, Rodrigo;Raina, Vinod;Abraham, Mirta;Medeiros Alencar, Victor Hugo;Badran, Atef;Bonfill, Xavier;Bradbury, Joan;Clarke, Michael;Collins, Rory;Davis, Susan R.;Delmestri, Antonella;Forbes, John F.;Haddad, Peiman;Hou, Ming-Feng;Inbar, Moshe;Khaled, Hussein;Kielanowska, Joanna;Kwan, Wing-Hong;Mathew, Beela S.;Mittra, Indraneel;Mueller, Bettina;Nicolucci, Antonio;Peralta, Octavio;Pernas, Fany;Petruzelka, Lubos;Pienkowski, Tadeusz;Radhika, Ramachandran;Rajan, Balakrishnan;Rubach, Maryna T.;Tort, Sera;Urrutia, Gerard;Valentini, Miriam;Wang, Yaochen;Peto, Richard
通讯作者：
Peto, Richard
影响因子：
3.7
作者：
Blume, Jessica J.;Halbach, Arndt;Plomann, Markus
通讯作者：
Plomann, Markus
DOI：
10.1073/pnas.1115188108
发表时间：
2011-11-22
影响因子：
11.1
作者：
Ariazi, Eric A.;Cunliffe, Heather E.;Jordan, V. Craig
通讯作者：
Jordan, V. Craig
影响因子：
5.3
作者：
Dahan, Jennifer;Nouet, Yann;Wei, Yu
通讯作者：
Wei, Yu