Lamb Justin, Ramaswamy Sridhar, Ford Heide L, Contreras Bernardo, Martinez Robert V, Kittrell Frances S, Zahnow Cynthia A, Patterson Nick, Golub Todd R, Ewen Mark E
Departments of Medical Oncology and Medicine, Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
Cell. 2003 Aug 8;114(3):323-34. doi: 10.1016/s0092-8674(03)00570-1.
Here we describe how patterns of gene expression in human tumors have been deconvoluted to reveal a mechanism of action for the cyclin D1 oncogene. Computational analysis of the expression patterns of thousands of genes across hundreds of tumor specimens suggested that a transcription factor, C/EBPbeta/Nf-Il6, participates in the consequences of cyclin D1 overexpression. Functional analyses confirmed the involvement of C/EBPbeta in the regulation of genes affected by cyclin D1 and established this protein as an indispensable effector of a potentially important facet of cyclin D1 biology. This work demonstrates that tumor gene expression databases can be used to study the function of a human oncogene in situ.
在此,我们描述了如何对人类肿瘤中的基因表达模式进行反卷积分析,以揭示细胞周期蛋白D1癌基因的作用机制。对数百个肿瘤样本中数千个基因的表达模式进行的计算分析表明,一种转录因子C/EBPβ/Nf-Il6参与了细胞周期蛋白D1过表达的后果。功能分析证实了C/EBPβ参与了受细胞周期蛋白D1影响的基因的调控,并将该蛋白确立为细胞周期蛋白D1生物学潜在重要方面不可或缺的效应因子。这项工作表明,肿瘤基因表达数据库可用于原位研究人类癌基因的功能。