The Ets protein PEA3 suppresses HER-2/neu overexpression and inhibits tumorigenesis

被引：148

作者：

Xing, XM

Wang, SC

Xia, WY

Zou, YY

Shao, RP

Kwong, KY

Yu, ZM

Zhang, S

Miller, S

Huang, L

Hung, MC

机构：

[1] Univ Texas, MD Anderson Canc Ctr, Dept Canc Biol, Sect Mol Cell Biol, Houston, TX 77030 USA

[2] Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15261 USA

来源：

NATURE MEDICINE | 2000年 / 6卷 / 02期

关键词：

D O I：

10.1038/72294

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：

Because HER-2/neu overexpression is important in cancer development, we looked for a method of suppressing the cell transformation mediated by HER-2/neu overexpression. We have identified that the DNA-binding protein PEA3, which is encoded by a previously isolated gene of the ets family, specifically targeted a DNA sequence on the HER-2/neu promoter and downregulated the promoter activity. Expression of PEA3 resulted in preferential inhibition of cell growth and tumor development of HER-2/neu-overexpressing cancer cells. This is a new approach to targeting HER-2/neu overexpression and also provides a rationale to the design for repressors of diseases caused by overexpression of pathogenic genes.

引用

页码：189 / 195

页数：7

共 48 条

[1]

Baert JL, 1997, INT J CANCER, V70, P590, DOI 10.1002/(SICI)1097-0215(19970304)70:5<590::AID-IJC17>3.0.CO

[2]

2-H

[3]

Baselga J, 1998, CANCER RES, V58, P2825

[4] HER2/Neu and the Ets transcription activator PEA3 are coordinately upregulated in human breast cancer [J].

Benz, CC ;

OHagan, RC ;

Richter, B ;

Scott, GK ;

Chang, CH ;

Xiong, XH ;

Chew, K ;

Ljung, BM ;

Edgerton, S ;

Thor, A ;

Hassell, JA .

ONCOGENE, 1997, 15 (13) :1513-1525

[5]

BENZ CC, 1993, BREAST CANCER RES TR, V24, P85

[6]

BERCHUCK A, 1990, CANCER RES, V50, P4087

[7] BIOLOGICALLY-ACTIVE MUTANTS WITH DELETIONS IN THE V-MOS-ONCOGENE ASSAYED WITH RETROVIRAL VECTORS [J].

BOLD, RJ ;

DONOGHUE, DJ .

MOLECULAR AND CELLULAR BIOLOGY, 1985, 5 (11) :3131-3138

[8]

BUTTICE G, 1993, J BIOL CHEM, V268, P7196

[9] The tumor suppression activity of E1A in HER-2/neu-overexpressing breast cancer [J].

Chang, JY ;

Xia, WY ;

Shao, RP ;

Sorgi, F ;

Hortobagyi, GN ;

Huang, L ;

Hung, MC .

ONCOGENE, 1997, 14 (05) :561-568

[10]

CHAZIN VR, 1992, ONCOGENE, V7, P1859

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