A functional Notch-survivin gene signature in basal breast cancer.
A functional Notch-survivin gene signature in basal breast cancer.
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DOI：
10.1186/bcr2200
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Altieri DC
中科院分区：
文献类型：
--
作者：
Lee CW;Simin K;Liu Q;Plescia J;Guha M;Khan A;Hsieh CC;Altieri DC
基底型或三阴性乳腺癌（缺乏雌激素受体、孕激素受体和人表皮生长因子受体-2表达）是一种目前尚无分子治疗的高危疾病。我们研究了可能适合于治疗干预的基底乳腺癌的遗传特征。我们通过免疫组化分析了一系列基底部乳腺癌患者中Notch-1胞内结构域和生存素的蛋白表达。对232例乳腺癌患者的微阵列mRNA数据库进行分层聚类和总体生存分析。对15个已发表的含有雌激素受体阴性或雌激素受体阳性样本的mRNA数据集进行共分离基因表达的荟萃分析。在雌激素受体阴性的MDA-MB-231乳腺癌细胞中进行质粒转染和基因沉默实验。与正常组织相比，发育信号调节因子Notch-1在乳腺癌中高表达，并与基础疾病分离。较高的Notch-1水平与逐渐缩短的总生存期相关，并与生存素表达增加相关，生存素是一种与干细胞活力有关的肿瘤相关细胞死亡和有丝分裂调节因子。Pearson相关系数分析表明，Notch-1和Survivin在基底层乳腺癌中共分离。在MDA-MB-231细胞中，Notch-1刺激增加存活素表达，而Notch沉默降低存活素水平。Notch-1-生存素功能基因标记是基底乳腺癌的标志，并可能有助于疾病的发病机制。目前在临床上的Notch和生存素的拮抗剂可以作为这些复发倾向患者的新型分子疗法进行测试。
Basal-type, or triple-negative, breast cancer (lacking estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 expression) is a high-risk disease for which no molecular therapies are currently available. We studied genetic signatures of basal breast cancer potentially suitable for therapeutic intervention. We analyzed protein expression of the Notch-1 intracellular domain and survivin by immunohistochemistry in a series of basal breast cancer patients. A hierarchical clustering and overall survival analysis was carried out on a microarray mRNA database of 232 breast cancer patients. Fifteen published mRNA datasets containing estrogen receptor-negative or estrogen receptor-positive samples were subjected to meta-analysis for co-segregated gene expression. Experiments of plasmid transfection and gene silencing were carried out in estrogen receptor-negative MDA-MB-231 breast cancer cells. The developmental signaling regulator Notch-1 was highly expressed in breast cancer, compared with normal tissue, and was segregated with basal disease. Higher Notch-1 levels correlated with progressively abbreviated overall survival, and with increased expression of survivin, a tumor-associated cell death and mitotic regulator implicated in stem cell viability. Analysis of Pearson's correlation coefficient indicated that Notch-1 and survivin co-segregated in basal breast cancer. Notch-1 stimulation in MDA-MB-231 cells increased survivin expression, whereas silencing Notch reduced survivin levels. A Notch-1–survivin functional gene signature is a hallmark of basal breast cancer, and may contribute to disease pathogenesis. Antagonists of Notch and survivin currently in the clinic may be tested as novel molecular therapy for these recurrence-prone patients.
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影响因子：
12.3
作者：
Herschkowitz JI;Simin K;Weigman VJ;Mikaelian I;Usary J;Hu Z;Rasmussen KE;Jones LP;Assefnia S;Chandrasekharan S;Backlund MG;Yin Y;Khramtsov AI;Bastein R;Quackenbush J;Glazer RI;Brown PH;Green JE;Kopelovich L;Furth PA;Palazzo JP;Olopade OI;Bernard PS;Churchill GA;Van Dyke T;Perou CM
通讯作者：
Perou CM
影响因子：
15.9
作者：
Dohi, T;Beltrami, E;Altieri, DC
通讯作者：
Altieri, DC
影响因子：
11.2
作者：
Ghosh, Jagadish C.;Dohi, Takehiko;Altieri, Dario C.
通讯作者：
Altieri, Dario C.
影响因子：
2.6
作者：
Hopfer, Olaf;Komor, Martina;Hofmann, Wolf-Karsten
通讯作者：
Hofmann, Wolf-Karsten
DOI：
10.1016/0197-2456(86)90046-2
发表时间：
1986-09-01
期刊：
CONTROLLED CLINICAL TRIALS
影响因子：
--
作者：
DERSIMONIAN, R;LAIRD, N
通讯作者：
LAIRD, N