Species- and cell type-specific requirements for cellular transformation
Species- and cell type-specific requirements for cellular transformation
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DOI：
10.1016/j.ccr.2004.07.009
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发表时间：
2004-08-01
期刊：
影响因子：
50.3
通讯作者：
Weinberg, RA
中科院分区：
文献类型：
--
作者：
Rangarajan, A;Hong, SJ;Weinberg, RA
最近的证据表明，人类细胞需要更多的遗传变化，肿瘤转化比他们的小鼠同行。然而，从未对这些差异进行过精确的列举。我们已经确定，扰动的两个信号通路，涉及p53和Raf-enough正常小鼠成纤维细胞的致瘤性转换，而扰动的六个通路，涉及p53，pRb，PP 2A，端粒酶，Raf，和Ral-GEFs-需要为人类成纤维细胞。细胞类型特异性差异也存在于致瘤转化的要求中：永生化人成纤维细胞需要Raf和Ral-GEF的活化，人胚肾细胞需要PI 3 K和Ral-GEF的活化，人乳腺上皮细胞需要Raf、PI 3 K和Ral-GEF的活化。
Recent evidence suggests that human cells require more genetic changes for neoplastic transformation than do their murine counterparts. However, a precise enumeration of these differences has never been undertaken. We have determined that perturbation of two signaling pathways-involving p53 and Raf-suffices for the tumorigenic conversion of normal murine fibroblasts, while perturbation of six pathways-involving p53, pRb, PP2A, telomerase, Raf, and Ral-GEFs-is needed for human fibroblasts. Cell type-specific differences also exist in the requirements for tumorigenic transformation: immortalized human fibroblasts require the activation of Raf and Ral-GEFs, human embryonic kidney cells require the activation of PI3K and Ral-GEFs, and human mammary epithelial cells require the activation of Raf, PI3K, and Ral-GEFs.