Gene expression profiling of leukemic cells and primary thymocytes predicts a signature for apoptotic sensitivity to glucocorticoids.
Gene expression profiling of leukemic cells and primary thymocytes predicts a signature for apoptotic sensitivity to glucocorticoids.
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白血病细胞和原发性胸腺细胞的基因表达分析预测了对糖皮质激素凋亡敏感性的特征。
DOI：
10.1186/1475-2867-7-18
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发表时间：
2007-11-28
影响因子：
5.8
通讯作者：
Thompson, E. Brad
中科院分区：
文献类型：
--
作者：
Miller, Aaron L.;Komak, Spogmai;Webb, M. Scott;Leiter, Edward H.;Thompson, E. Brad
糖皮质激素（GC）在旨在对抗各种形式的血液恶性肿瘤的治疗策略中发挥着不可或缺的作用。GC也是免疫系统的强有力抑制剂，通过调节适当的细胞因子和引起未成熟胸腺细胞的凋亡。通过激活糖皮质激素受体（GR），GC通过在凋亡酶激活之前的一段时间内复杂的相互作用的基因网络的转录调节引起凋亡。在这项研究中，我们使用微阵列技术来确定是否几种不同类型的血液细胞，所有敏感的GC诱发的细胞凋亡，将确定一组共同的调控基因。我们使用一组血液细胞比较了用两种有效的合成GC，地塞米松（Dex）和可替唑（CVZ）治疗后的基因表达特征。儿童CD 4 +/CD 8 + T细胞白血病由3个CEM克隆代表：两个对Dex敏感，CEM-C7-14和CEM-C1-6，一个耐药，CEM-C1-15。当通过几种处理使CEM-C1-15对GC敏感时，也对CEM-C1-15进行了检测。GC敏感的儿童B细胞白血病以SUP-B15细胞系为代表，成人B细胞白血病以RS 4;11细胞为代表。Kasumi-1细胞是罕见的右旋糖酐敏感性急性髓细胞白血病（AML）的一个例子。为了测试恶性细胞基因组中相关性的一般性，我们比较了GC对小鼠非转化胸腺细胞的影响。我们确定了一组基因调控GC在所有GC敏感的恶性细胞。其中一部分也在胸腺细胞中受到调节。因为我们知道高度Dex抗性的CEM-C1-15细胞可以被CVZ杀死，所以我们用后一种类固醇测试了这些细胞，再次发现许多相同的基因现在被调节，就像在固有的GC敏感细胞中一样。当我们用毛喉素（FSK）处理将Dex抗性克隆转化为Dex敏感克隆以激活腺苷酸环化酶/蛋白激酶A途径（PKA）时，也得到了相同的结果。我们的研究结果已经确定了一些血液恶性肿瘤细胞中与GC敏感性相关的基因。其中一些在正常小鼠胸腺细胞中也受到调节。
Glucocorticoids (GC's) play an integral role in treatment strategies designed to combat various forms of hematological malignancies. GCs also are powerful inhibitors of the immune system, through regulation of appropriate cytokines and by causing apoptosis of immature thymocytes. By activating the glucocorticoid receptor (GR), GCs evoke apoptosis through transcriptional regulation of a complex, interactive gene network over a period of time preceding activation of the apoptotic enzymes. In this study we used microarray technology to determine whether several disparate types of hematologic cells, all sensitive to GC-evoked apoptosis, would identify a common set of regulated genes. We compared gene expression signatures after treatment with two potent synthetic GCs, dexamethasone (Dex) and cortivazol (CVZ) using a panel of hematologic cells. Pediatric CD4+/CD8+ T-cell leukemia was represented by 3 CEM clones: two sensitive, CEM-C7–14 and CEM-C1–6, and one resistant, CEM-C1–15, to Dex. CEM-C1–15 was also tested when rendered GC-sensitive by several treatments. GC-sensitive pediatric B-cell leukemia was represented by the SUP-B15 line and adult B-cell leukemia by RS4;11 cells. Kasumi-1 cells gave an example of the rare Dex-sensitive acute myeloblastic leukemia (AML). To test the generality of the correlations in malignant cell gene sets, we compared with GC effects on mouse non-transformed thymocytes. We identified a set of genes regulated by GCs in all GC-sensitive malignant cells. A portion of these were also regulated in the thymocytes. Because we knew that the highly Dex-resistant CEM-C1–15 cells could be killed by CVZ, we tested these cells with the latter steroid and again found that many of the same genes were now regulated as in the inherently GC-sensitive cells. The same result was obtained when we converted the Dex-resistant clone to Dex-sensitive by treatment with forskolin (FSK), to activate the adenyl cyclase/protein kinase A pathway (PKA). Our results have identified small sets of genes that correlate with GC-sensitivity in cells from several hematologic malignancies. Some of these are also regulated in normal mouse thymocytes.
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影响因子：
20.3
作者：
Bachmann, PS;Gorman, R;Lock, RB
通讯作者：
Lock, RB
影响因子：
4.8
作者：
Kim, Young Sun;Cho, Kyung-Ok;Cho, Young-Jin
通讯作者：
Cho, Young-Jin
影响因子：
--
作者：
Miller, AL;Webb, MS;Thompson, EB
通讯作者：
Thompson, EB
影响因子：
4.8
作者：
Abrams, MT;Robertson, NM;Wickstrom, E
通讯作者：
Wickstrom, E
DOI：
10.1124/jpet.106.108480
发表时间：
2006-11-01
影响因子：
3.5
作者：
Bianchini, Rodolfo;Nocentini, Giuseppe;Riccardi, Carlo
通讯作者：
Riccardi, Carlo