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一种由人类癌症基因表达模式所编码的细胞周期蛋白D1作用机制。

A mechanism of cyclin D1 action encoded in the patterns of gene expression in human cancer.

作者信息

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

机构信息

Departments of Medical Oncology and Medicine, Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.

出版信息

Cell. 2003 Aug 8;114(3):323-34. doi: 10.1016/s0092-8674(03)00570-1.

Abstract

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.

摘要

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。

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