在小鼠单细胞瘤中,GM-CSF和瘤基因mRNA的稳定性在转基因中被独立调节
1Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, New Jersey 08540.
Cell
|December 23, 1988
概括
瘤细胞通过瘤特异性因子稳定粒细胞 - 巨细胞殖民地刺激因子 (GM-CSF) 使者RNA (mRNA). 这种mRNA循环调节突出了细胞内AU丰富元素的差异性识别.
科学领域:
- 分子生物学分子生物学
- 癌症生物学 癌症生物学
- 基因规则 基因规则
背景情况:
- mRNA循环是基因表达的关键调节机制,特别是在淋巴基因和瘤基因.
- 调节不良的mRNA稳定性可能导致癌症等疾病.
- 单细胞瘤模型表现出由于mRNA稳定而具有构成性激活的粒细胞 - 巨细胞殖民地刺激因子 (GM-CSF) 表达.
研究的目的:
- 在单细胞瘤中研究基因转基因-CSFmRNA稳定背后的分子机制.
- 为了确定稳定是由于GM-CSF基因或跨作用因子的改变.
- 探索癌细胞中mRNA循环信号的差异识别.
主要方法:
- 构建融合基因,将GM-CSF的3'未翻译区域 (UTR) 与一个新记者基因联系起来.
- 分析瘤细胞和其他细胞类型中记者mRNA的周转率.
- 将GM-CSF mRNA融合的稳定性与c-myc和c-fos mRNA融合的稳定性进行比较.
主要成果:
- 转基因-CSF的mRNA稳定是由瘤特异性转基因作用因子介导的,而不是转基因-CSF基因本身的变化.
- 含有c-myc和c-fos的3' UTRs的记者mRNA在所有测试细胞,包括瘤细胞中都表现出快速的循环.
- 这些发现表明,在相同的细胞环境中,AU丰富的mRNA循环信号的差异识别.
结论:
- 在这种单细胞瘤中,瘤特异性因素负责GM-CSFmRNA的构成性稳定.
- 细胞机械不同地识别和响应调节mRNA周转的富含AU元素.
- 这项研究提供了有关癌症转录后基因调节的见解,并确定了潜在的治疗点.
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