Ellwood-Yen Katharine, Graeber Thomas G, Wongvipat John, Iruela-Arispe M Luisa, Zhang JianFeng, Matusik Robert, Thomas George V, Sawyers Charles L
Department of Medicine, and Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Cancer Cell. 2003 Sep;4(3):223-38. doi: 10.1016/s1535-6108(03)00197-1.
Increased Myc gene copy number is observed in human prostate cancer. To define Myc's functional role, we generated transgenic mice expressing human c-Myc in the mouse prostate. All mice developed murine prostatic intraepithelial neoplasia followed by invasive adenocarcinoma. Microarray-based expression profiling identified a Myc prostate cancer expression signature, which included the putative human tumor suppressor NXK3.1. Human prostate tumor databases revealed modules of human genes that varied in concert with the Myc prostate cancer signature. This module includes the Pim-1 kinase, a gene known to cooperate with Myc in tumorigenesis, and defines a subset of human, "Myc-like" human cancers. This approach illustrates how genomic technologies can be applied to mouse cancer models to guide evaluation of human tumor databases.
在人类前列腺癌中观察到Myc基因拷贝数增加。为了确定Myc的功能作用，我们构建了在小鼠前列腺中表达人类c-Myc的转基因小鼠。所有小鼠均发展为小鼠前列腺上皮内瘤变，随后发展为浸润性腺癌。基于微阵列的表达谱分析确定了一种Myc前列腺癌表达特征，其中包括假定的人类肿瘤抑制因子NXK3.1。人类前列腺肿瘤数据库揭示了与Myc前列腺癌特征协同变化的人类基因模块。该模块包括Pim-1激酶，这是一种已知在肿瘤发生过程中与Myc协同作用的基因，并定义了一部分人类“Myc样”癌症。这种方法说明了如何将基因组技术应用于小鼠癌症模型，以指导对人类肿瘤数据库的评估。
