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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Kinase Requirements In Human Cells: I. Comparing Kinase Requirements Across Various Cell Types
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Kinase Requirements In Human Cells: I. Comparing Kinase Requirements Across Various Cell Types

机译:人类细胞中的激酶需求:I.比较各种细胞类型的激酶需求

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shRNA loss-of-function screens were used to identify kinases that were rate-limiting for promoting cell proliferation and survival. Here, we study the differences in kinase requirements among various human cells, including freshly prepared primary cells, isogenic cells, immortalized cells, and cancer cell lines. Closely related patterns of kinase requirements among the various cell types were observed in three cases: (ⅰ) in repeat experiments using the same cells, (ⅱ) with multiple populations of freshly prepared primary epithelial cells isolated from the same tissue source, and (ⅲ) between nearly isogenic cells that differ from each other by the expression of a single gene. Other commonly used cancer cell lines were distinct from one another, even when they were isolated from similar tumor types. Even primary cells of different lineages isolated from the same tissue source showed many differences. The differences in kinase requirements among cell lines observed in this study suggest that the control of proliferation and survival may be significantly different between cell lines and that simple comparisons from any one cell to another may be misleading. Although the regulation of cell proliferation and survival are heavily studied areas, we did not see a bias in these screens toward the identification of previously known and well studied kinases, suggesting that our knowledge of molecular events in these areas is still meager.
机译:shRNA功能丧失筛选用于鉴定速率限制促进细胞增殖和存活的激酶。在这里,我们研究了包括新鲜制备的原代细胞,等基因细胞,永生细胞和癌细胞系在内的各种人类细胞之间激酶需求的差异。在三种情况下,观察到了各种细胞类型之间的激酶需求密切相关模式:(ⅰ)在使用相同细胞的重复实验中进行;(with)从同一组织来源分离的多个新鲜制备的原代上皮细胞群体;和)之间的异同基因细胞之间存在差异,它们之间通过单个基因的表达而彼此不同。其他常用的癌细胞系彼此不同,即使它们是从相似的肿瘤类型中分离出来的也是如此。从同一组织来源分离的不同谱系的原代细胞也显示出许多差异。在这项研究中观察到的细胞系之间激酶需求的差异表明,细胞系之间增殖和存活的控制可能显着不同,从任何一个细胞到另一个细胞的简单比较可能会产生误导。尽管细胞增殖和存活的调控是研究广泛的领域,但我们在这些筛选中并未发现偏向于鉴定先前已知和研究充分的激酶,这表明我们对这些领域中分子事件的了解仍然很少。

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