Webb M Scott, Miller Aaron L, Johnson Betty H, Fofanov Yuriy, Li Tongbin, Wood Thomas G, Thompson E Brad
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0645, USA.
J Steroid Biochem Mol Biol. 2003 Jun;85(2-5):183-93. doi: 10.1016/s0960-0760(03)00194-8.
To discover the genes responsible for the apoptosis evoked by glucocorticoids in leukemic lymphoid cells, we have begun gene array analysis on microchips. Three clones of CEM cells were compared: C7-14, C1-15 and C1-6. C7-14 and C1-15 are subclones from the original clones C7 (sensitive to apoptosis by glucocorticoids) and C1 (resistant). C1-6 is a spontaneous revertant to sensitivity from the C1 clone. Previously we presented data on the sets of genes whose expression is altered in these cell clones after 20 h exposure to dexamethasone (Dex). The two sensitive clones, which respond by undergoing apoptosis starting about 24h after Dex is added, both showed >2.5-fold induction of 39 genes and 2-fold reduction of expressed levels from 21 genes. C1-15, the resistant clone, showed alterations in a separate set of genes. In this paper, we present further analysis of the data on genes regulated in these cell clones after 20 h Dex and compare them with the genes regulated after 12h Dex. Some, but not all the genes found altered at 20 h are altered at 12h, consistent with our hypothesis that sequential gene regulation eventually provokes full apoptosis. We also compare the levels of basal gene expression in the three clones. At the basal level no single gene stands out, but small sets of genes differ >2-fold in basal expression between the two sensitive and the resistant clone. A number of the genes basally higher in the resistant clone are potentially anti-apoptotic. This is consistent with our hypothesis that the resistant cells have undergone a general shift in gene expression.
为了发现白血病淋巴细胞中糖皮质激素诱导凋亡相关的基因，我们开始了基因芯片的基因阵列分析。比较了CEM细胞的三个克隆：C7-14、C1-15和C1-6。C7-14和C1-15是原始克隆C7（对糖皮质激素诱导的凋亡敏感）和C1（抗性）的亚克隆。C1-6是C1克隆自发回复为敏感型的克隆。之前我们展示了这些细胞克隆在暴露于地塞米松（Dex）20小时后基因表达改变的数据集。两个敏感克隆在加入Dex后约24小时开始通过凋亡做出反应，它们均显示39个基因诱导超过2.5倍，21个基因表达水平降低2倍。抗性克隆C1-15在另一组基因中出现改变。在本文中，我们进一步分析了这些细胞克隆在Dex处理20小时后调控基因的数据，并将其与Dex处理12小时后调控的基因进行比较。一些（但不是全部）在20小时发现改变的基因在12小时也发生改变，这与我们的假设一致，即基因的顺序调控最终引发完全凋亡。我们还比较了三个克隆中基础基因表达水平。在基础水平上没有单个基因突出，但在两个敏感克隆和抗性克隆之间，少量基因的基础表达差异超过2倍。抗性克隆中基础表达较高的许多基因可能具有抗凋亡作用。这与我们的假设一致，即抗性细胞在基因表达上发生了普遍转变。
