Regulation of growth-related genes by interleukin-6 in murine myeloma cells
Regulation of growth-related genes by interleukin-6 in murine myeloma cells
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DOI：
10.1006/cyto.2002.1988
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发表时间：
2002-11-07
期刊：
影响因子：
3.8
通讯作者：
Lemieux, R
中科院分区：
文献类型：
--
作者：
Côté, S;Simard, C;Lemieux, R
白细胞介素-6（IL-6）是一种对几种造血细胞和其他正常细胞具有作用的多效性细胞因子，对肿瘤细胞如鼠浆细胞瘤和人骨髓瘤的生长和存活也很重要。利用11 A3杂交瘤细胞系的IL-6要求在体外增殖，我们使用消减抑制杂交（SSH），以确定其表达的刺激和/或抑制响应IL-6的基因。对100个任意挑选的消减cDNA克隆的北方印迹分析显示，11个mRNA的表达是IL-6调节的。其中，8个是已知编码多种蛋白质的基因，所述蛋白质例如酶（PCK、MTDNI）、结构蛋白质（原弹性蛋白）、转录调节因子（BRG 1）和参与细胞分裂控制的蛋白质（细胞周期蛋白A、OAZi）或细胞信号传导的蛋白质（P1 X、TOPKlPBK）。最近鉴定的MAPKK样蛋白激酶TOPKlPBK基因代表了可能的候选IL-6靶基因，如其在由短暂IL-6脉冲诱导生长的杂交瘤细胞中显著上调表达所表明的。本研究中鉴定的生长相关基因的多样性进一步强调了IL-6在调节骨髓瘤细胞扩增中的中心作用，除了其先前证明的在抑制细胞凋亡中的作用。(C)2002爱思唯尔科技有限公司版权所有。
Interleukin-6 (IL-6), a pleiotropic cytokine with effects on several hematopoietic and other normal cells, is also important for the growth and survival of tumor cells such as murine plasmacytomas and human myelomas. Exploiting the 11A3 hybridoma cell line for its IL-6 requirement to proliferate in vitro, we used subtractive suppression hybridization (SSH) to identify genes whose expression is stimulated and/or repressed in response to IL-6. Northern blot analysis of 100 arbitrarily picked subtracted cDNA clones revealed that expression of 11 mRNAs were IL-6-modulated. Among these, eight were genes known to encode a variety of proteins such as enzymes (PCK, MTDNI), structural proteins (Tropoelastin), transcriptional regulators (BRG1) and proteins involved in cell division control (Cyclin A, OAZi) or cell signaling (P1X, TOPKlPBK). The recently identified MAPKK-like protein kinase TOPKlPBK gene represents a likely candidate IL-6 target gene as suggested by its significant up-regulated expression in hybridoma cells induced to grow by a brief IL-6 pulse. The diversity of growth-related genes identified in this study further emphasizes the central role of IL-6 in the regulation of myeloma cell expansion in addition to its previously demonstrated role in the inhibition of apoptosis. (C) 2002 Elsevier Science Ltd. All rights reserved.