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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: Iv. Differential Kinase Requirements In Cervical And Renal Human Tumor Cell Lines
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Kinase Requirements In Human Cells: Iv. Differential Kinase Requirements In Cervical And Renal Human Tumor Cell Lines

机译：人细胞中的激酶要求：子宫颈和肾脏人类肿瘤细胞系中的差异激酶需求

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摘要

Functional differences among human cells have been difficult to identify by standard biochemical methods. Loss-of-function shRNA screens provide an unbiased method to compare protein requirements across cell lines. In previous work, we have studied kinase requirements in two settings, either among a panel of cells from numerous tissues or between two cell lines that differ only by the expression of a chosen oncoprotein or tumor suppressor protein. Here we examine the patterns of kinase requirements between two unrelated cells, the cervical carcinoma cell line HeLa and the renal carcinoma cell line 786-O. By using time courses of cell proliferation after shRNA transduction and by introducing different levels of the shRNAs, we were able to carefully compare the kinase requirements. These comparisons identified 10 kinases that were required in HeLa but not 786-O, and 5 kinases that were required in 786-O but not HeLa. The patterns of growth inhibition due to particular sets of shRNAs in a tumor cell line were shown to be similar in some but not all cell lines derived from the same tissue-specific cancer type. Differential kinase requirements promise to be useful in distinguishing important cell-to-cell functional variations and may lead to the identification of fingerprints for different physiological cell states.
机译：人类细胞之间的功能差异很难通过标准的生化方法来鉴定。功能丧失的shRNA筛选提供了一种公正的方法来比较跨细胞系的蛋白质需求。在以前的工作中，我们已经研究了两种情况下的激酶需求，这两种情况是来自众多组织的一组细胞之间，或者是两种细胞系之间的区别，两者之间的区别仅在于所选癌蛋白或肿瘤抑制蛋白的表达不同。在这里，我们检查了两个无关细胞，宫颈癌细胞系HeLa和肾癌细胞系786-O之间的激酶需求模式。通过使用shRNA转导后细胞增殖的时程并通过引入不同水平的shRNA，我们能够仔细比较激酶的需求。这些比较确定了HeLa所需的10种激酶，而不是786-O，而786-O所需的5种激酶，而不是HeLa。在某些但并非所有源自相同组织特异性癌症类型的细胞系中，显示出由于肿瘤细胞系中特定组的shRNA而导致的生长抑制模式相似。差异激酶要求有望用于区分重要的细胞间功能变异，并可能导致鉴定不同生理细胞状态的指纹。

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