C/EBPβ at the core of the TGFβ cytostatic response and its evasion in metastatic breast cancer cells

被引：229

作者：

Gomis, Roger R.

Alarcon, Claudio

Nadal, Cristina

Van Poznak, Catherine

Massague, Joan ^{[1
]}

机构：

[1] Howard Hughes Med Inst, Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10021 USA

[2] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA

来源：

CANCER CELL | 2006年 / 10卷 / 03期

关键词：

D O I：

10.1016/j.ccr.2006.07.019

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Breast cancers may evade the growth-inhibitory action of TGFO by accumulating defects of unknown nature that selectively eliminate cytostatic gene responses. We found the transcription factor C/EBPO to be essential for TGFO induction of the cell cycle inhibitor p151NK4b by a FoxO-Smad complex and repression of c-MYC by an E2F4/5-Smad complex in human epithelial cells. These cytostatic responses are selectively missing in metastatic breast cancer cells from half of the patients that we tested. The basis for this loss was traced to an excess of the C/EBPO inhibitory isoform LIP. We suggest that C/EBPO plays a key role in the coordination of TGFO cytostatic gene responses, and its malfunction may trigger evasion of these responses in breast cancer.

引用

页码：203 / 214

页数：12

共 58 条

[1] Prospective identification of tumorigenic breast cancer cells [J].

Al-Hajj, M ;

Wicha, MS ;

Benito-Hernandez, A ;

Morrison, SJ ;

Clarke, MF .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (07) :3983-3988

[2] Epidermal growth factor receptor stimulation activates the RNA bindin protein CUG-BP1 and increases expression of C/EBPβ-LIP in mammary epithelial cells [J].

Baldwin, BR ;

Timchenko, NA ;

Zahnow, CA .

MOLECULAR AND CELLULAR BIOLOGY, 2004, 24 (09) :3682-3691

[3] Essential requirement of CCAAT/enhancer binding proteins in embryogenesis [J].

Bégay, V ;

Smink, J ;

Leutz, A .

MOLECULAR AND CELLULAR BIOLOGY, 2004, 24 (22) :9744-9751

[4] Stable suppression of tumorigenicity by virus-mediated RNA interference [J].

Brummelkamp, TR ;

Bernards, R ;

Agami, R .

CANCER CELL, 2002, 2 (03) :243-247

[5] Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase [J].

Brunet, A ;

Sweeney, LB ;

Sturgill, JF ;

Chua, KF ;

Greer, PL ;

Lin, YX ;

Tran, H ;

Ross, SE ;

Mostoslavsky, R ;

Cohen, HY ;

Hu, LS ;

Cheng, HL ;

Jedrychowski, MP ;

Gygi, SP ;

Sinclair, DA ;

Alt, FW ;

Greenberg, ME .

SCIENCE, 2004, 303 (5666) :2011-2015

[6] Smad4/DPC4 silencing and hyperactive Ras jointly disrupt transforming growth factor-β antiproliferative responses in colon cancer cells [J].

Calonge, MJ ;

Massagué, J .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (47) :33637-33643

[7]

CARCAMO J, 1995, MOL CELL BIOL, V15, P1573

[8] E2F4/5 and p107 as Smad cofactors linking the TGFβ receptor to c-myc repression [J].

Chen, CR ;

Kang, YB ;

Siegel, PM ;

Massagué, J .

CELL, 2002, 110 (01) :19-32

[9] Defective repression of c-myc in breast cancer cells:: A loss at the core of the transforming growth factor β growth arrest program [J].

Chen, CR ;

Kang, YB ;

Massagué, J .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (03) :992-999

[10] Transforming growth factor-β inhibits adipocyte differentiation by Smad3 interacting with CCAAT/enhancer-binding protein (C/EBP) and repressing C/EBP transactivation function [J].

Choy, L ;

Derynck, R .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (11) :9609-9619

← 1 2 3 4 5 6 →