ETS 转录因子 MEF 和 ERG 的致癌作用。
The oncogenic role of the ETS transcription factors MEF and ERG.
机构信息
Molecular Pharmacology and Chemistry Program of the Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, NY, USA.
出版信息
Cell Cycle. 2010 Sep 1;9(17):3457-9. doi: 10.4161/cc.9.17.13000. Epub 2010 Sep 13.
Abstract
Several ETS transcription factors, including MEF/ELF4 and ERG, can function as oncogenes and are overexpressed in human cancer. MEF cooperates in tumorigenesis in retroviral insertional mutagenesis-based mouse models of cancer and MEF is overexpressed in human lymphoma and ovarian cancer tissues via unknown mechanisms. ERG (Ets related gene) overexpression or increased activity has been found in various human cancers, including sarcomas, acute myeloid leukemia and prostate cancer, where the ERG gene is rearranged due to chromosomal translocations. We have been examining how MEF functions as an oncogene and recently showed that MEF can cooperate with H-Ras(G12V) and can inhibit both p53 and p16 expression thereby promoting transformation. In fact, in cells lacking p53, the absence of Mef abrogates H-Ras(G12V)-induced transformation of mouse embryonic fibroblasts, at least in part due to increased p16 expression. We discuss the known mechanisms by which the ETS transcription factors MEF and ERG contribute to the malignant transformation of cells.
摘要
几种 ETS 转录因子，包括 MEF/ELF4 和 ERG，可作为癌基因发挥作用，并在人类癌症中过度表达。MEF 在逆转录病毒插入诱变的癌症小鼠模型中协同致癌，并且通过未知机制在人类淋巴瘤和卵巢癌组织中过表达。在各种人类癌症中，包括肉瘤、急性髓性白血病和前列腺癌中，都发现 ERG（Ets 相关基因）过表达或活性增加，而 ERG 基因由于染色体易位而重排。我们一直在研究 MEF 如何作为癌基因发挥作用，最近表明 MEF 可以与 H-Ras(G12V) 合作，并可以抑制 p53 和 p16 的表达，从而促进转化。事实上，在缺乏 p53 的细胞中，Mef 的缺失会消除 H-Ras(G12V)诱导的小鼠胚胎成纤维细胞转化，至少部分原因是 p16 表达增加。我们讨论了 ETS 转录因子 MEF 和 ERG 促进细胞恶性转化的已知机制。
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Proc Natl Acad Sci U S A. 2009 Jul 28;106(30):12465-70. doi: 10.1073/pnas.0905931106. Epub 2009 Jul 10.
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ELF4/MEF activates MDM2 expression and blocks oncogene-induced p16 activation to promote transformation.ELF4/MEF激活MDM2表达并阻断癌基因诱导的p16激活以促进细胞转化。
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