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

被引：337

作者：

Lamb, J

Ramaswamy, S

Ford, HL

Contreras, B

Martinez, RV

Kittrell, FS

Zahnow, CA

Patterson, N

Golub, TR

Ewen, ME

机构：

[1] Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dept Canc Biol, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Dept Biochem, Boston, MA 02115 USA

[5] Harvard Univ, Sch Med, Dept Mol Pharmacol, Boston, MA 02115 USA

[6] Harvard Univ, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA

[7] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

[8] MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA

[9] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

[10] Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD 21231 USA

来源：

CELL | 2003年 / 114卷 / 03期

关键词：

D O I：

10.1016/S0092-8674(03)00570-1

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-II6, participates in the consequences of cyclin Di 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.

引用

页码：323 / 334

页数：12

共 48 条

[1] Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling [J].

Alizadeh, AA ;

Eisen, MB ;

Davis, RE ;

Ma, C ;

Lossos, IS ;

Rosenwald, A ;

Boldrick, JG ;

Sabet, H ;

Tran, T ;

Yu, X ;

Powell, JI ;

Yang, LM ;

Marti, GE ;

Moore, T ;

Hudson, J ;

Lu, LS ;

Lewis, DB ;

Tibshirani, R ;

Sherlock, G ;

Chan, WC ;

Greiner, TC ;

Weisenburger, DD ;

Armitage, JO ;

Warnke, R ;

Levy, R ;

Wilson, W ;

Grever, MR ;

Byrd, JC ;

Botstein, D ;

Brown, PO ;

Staudt, LM .

NATURE, 2000, 403 (6769) :503-511

[2] Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses [J].

Bhattacharjee, A ;

Richards, WG ;

Staunton, J ;

Li, C ;

Monti, S ;

Vasa, P ;

Ladd, C ;

Beheshti, J ;

Bueno, R ;

Gillette, M ;

Loda, M ;

Weber, G ;

Mark, EJ ;

Lander, ES ;

Wong, W ;

Johnson, BE ;

Golub, TR ;

Sugarbaker, DJ ;

Meyerson, M .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (24) :13790-13795

[3] Cyclin D1 represses STAT3 activation through a Cdk4-independent mechanism [J].

Bienvenu, F ;

Gascan, H ;

Coqueret, O .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (20) :16840-16847

[4] Exploring the metabolic and genetic control of gene expression on a genomic scale [J].

DeRisi, JL ;

Iyer, VR ;

Brown, PO .

SCIENCE, 1997, 278 (5338) :680-686

[5] A LIVER-ENRICHED TRANSCRIPTIONAL ACTIVATOR PROTEIN, LAP, AND A TRANSCRIPTIONAL INHIBITORY PROTEIN, LIP, ARE TRANSLATED FROM THE SAME MESSENGER-RNA [J].

DESCOMBES, P ;

SCHIBLER, U .

CELL, 1991, 67 (03) :569-579

[6]

Desprez Pierre-Yves, 1993, Molecular and Cellular Differentiation, V1, P99

[7] The regulation of E2F by pRB-family proteins [J].

Dyson, N .

GENES & DEVELOPMENT, 1998, 12 (15) :2245-2262

[8]

GAUGITSCH HW, 1992, J BIOL CHEM, V267, P11267

[9] Molecular classification of cancer: Class discovery and class prediction by gene expression monitoring [J].

Golub, TR ;

Slonim, DK ;

Tamayo, P ;

Huard, C ;

Gaasenbeek, M ;

Mesirov, JP ;

Coller, H ;

Loh, ML ;

Downing, JR ;

Caligiuri, MA ;

Bloomfield, CD ;

Lander, ES .

SCIENCE, 1999, 286 (5439) :531-537

[10]

Hall M, 1996, ADV CANCER RES, V68, P67, DOI 10.1016/S0065-230X(08)60352-8

← 1 2 3 4 5 →