期刊
CANCER RESEARCH
卷 76, 期 12, 页码 3463-3472出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-16-0316
关键词
-
类别
资金
- European Community's Seventh Framework Programme (MODHEP consortium) [259743]
- European Research Council [268671]
- Italian Health Ministry [RF-2011-02346976]
- Italian Association for Cancer Research (AIRC) [13182]
- Structured International Post Doc program of the European School of Molecular Medicine
- Cancer Research UK [12077, 19013, 22585] Funding Source: researchfish
- European Research Council (ERC) [268671] Funding Source: European Research Council (ERC)
Tumors driven by activation of the transcription factor MYC generally show oncogene addiction. However, the gene expression programs that depend upon sustained MYC activity remain unknown. In this study, we employed a mouse model of liver carcinoma driven by a reversible tet-MYC transgene, combined with chromatin immunoprecipitation and gene expression profiling to identify MYC-dependent regulatory events. As previously reported, MYC-expressing mice exhibited hepatoblastoma- and hepatocellular carcinoma-like tumors, which regressed when MYC expression was suppressed. We further show that cellular transformation, and thus initiation of liver tumorigenesis, were impaired in mice harboring a MYC mutant unable to associate with the corepressor protein MIZ1 (ZBTB17). Notably, switching off the oncogene in advanced carcinomas revealed that MYC was required for the continuous activation and repression of distinct sets of genes, constituting no more than half of all genes deregulated during tumor progression and an even smaller subset of all MYC-bound genes. Altogether, our data provide the first detailed analysis of a MYC-dependent transcriptional program in a fully developed carcinoma and offer a guide to identifying the critical effectors contributing to MYC-driven tumor maintenance. (C) 2016 AACR.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据