David H. Koch Institute for Integrative Cancer Research,Department of Biology, Massachusetts Institute of Technology, Cambridge, USA.
Genes Dev. 2011 Jul 15;25(14):1470-5. doi: 10.1101/gad.2046711.
Small cell lung cancer (SCLC) is an aggressive cancer often diagnosed after it has metastasized. Despite the need to better understand this disease, SCLC remains poorly characterized at the molecular and genomic levels. Using a genetically engineered mouse model of SCLC driven by conditional deletion of Trp53 and Rb1 in the lung, we identified several frequent, high-magnitude focal DNA copy number alterations in SCLC. We uncovered amplification of a novel, oncogenic transcription factor, Nuclear factor I/B (Nfib), in the mouse SCLC model and in human SCLC. Functional studies indicate that NFIB regulates cell viability and proliferation during transformation.
小细胞肺癌(SCLC)是一种侵袭性癌症,通常在转移后才被诊断出来。尽管需要更好地了解这种疾病,但 SCLC 在分子和基因组水平上仍未得到充分描述。我们使用肺中条件性缺失 Trp53 和 Rb1 驱动的 SCLC 基因工程小鼠模型,鉴定出 SCLC 中几个频繁出现的高幅度局灶性 DNA 拷贝数改变。我们在小鼠 SCLC 模型和人类 SCLC 中发现了一种新型致癌转录因子核因子 I/B(NFIB)的扩增。功能研究表明,NFIB 在转化过程中调节细胞活力和增殖。