New model systems provide insights into Myc-induced transformation
New model systems provide insights into Myc-induced transformation
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DOI：
10.1038/onc.2011.88
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发表时间：
2011-08-01
期刊：
影响因子：
8
通讯作者：
Penn, L. Z.
中科院分区：
文献类型：
--
作者：
Wasylishen, A. R.;Stojanova, A.;Penn, L. Z.
Myc促进细胞转化的能力是公认的；然而，更好地了解Myc介导肿瘤发生的机制对于开发针对这种强大的癌蛋白的治疗方法至关重要。啮齿动物成纤维细胞的结构-功能研究为我们目前对这些机制的大部分了解提供了基础。为了建立这些方法，我们鉴定了三个新的Myc依赖转化的人类细胞系模型：MCF10A、SH-EP Tet21/N-Myc和LF1/TERT/LT/ST细胞。我们还在这些模型中评估了Myc家族蛋白(c-Myc和L-Myc)和一组N-末端结构域突变体(DMBII、W135E、T58A)促进非锚定生长的能力。综上所述，这些结果为该领域提供了三个新的基于人类细胞的模型来研究Myc的活性，强调了细胞背景的重要性，并挑战了Myc促进肿瘤发生的能力完全依赖于MBII的范式。Oncogene(2011年)30,37273734；doi：10.1038/onc.2011.88；2011年3月28日在线发布
The ability of Myc to promote cellular transformation is well established; however, a better understanding of the mechanisms through which Myc mediates tumorigenesis is essential for the development of therapeutic approaches to target this potent oncoprotein. Structure-function studies in rodent fibroblast cells have provided the basis for much of our current understanding of these mechanisms. To build on these approaches, we have characterized three novel human cell line models of Myc-dependent transformation: MCF10A, SH-EP Tet21/N-Myc, and LF1/TERT/LT/ST cells. We have also evaluated Myc family proteins (c-Myc and L-Myc), a naturally occurring isoform of Myc (MycS), and a set of N-terminal domain mutants (DMBII, W135E, T58A) for their ability to promote anchorage-independent growth in these models. Taken together, these results provide the field with three new human cell-based models to study Myc activity, highlight the importance of cellular context, and challenge the paradigm that the ability of Myc to promote tumorigenesis is exclusively MBII-dependent. Oncogene (2011) 30, 3727-3734; doi:10.1038/onc.2011.88; published online 28 March 2011