The LIM-domain protein Lmo2 is a key regulator of tumour angiogenesis: a new anti-angiogenesis drug target

被引：45

作者：

Yamada, Y ^{[1
]}

Pannell, R ^{[1
]}

Forster, A ^{[1
]}

Rabbitts, TH ^{[1
]}

机构：

[1] Med Res Council Lab Mol Biol, Cambridge CB2 2QH, England

来源：

ONCOGENE | 2002年 / 21卷 / 09期

关键词：

transcriptional regulation; tumour angiogenesis; chromosomal translocation; endothelium; cancer; neo-vascularization;

D O I：

10.1038/sj.onc.1205285

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：

The growth of solid tumours requires a blood supply provided by re-modeling of existing blood vessel endothelium (angiogenesis). Little is known about transcription regulators which are specific for the control of tumour angiogenesis. The proto-oncogene LM02 encodes a LIM domain transcription regulator which controls angiogenesis during mouse embryogenesis where it regulates remodelling of the capillary network into mature vessels. We now show that Lmo2 expression is augmented in tumour endothelium such as mouse thymomas and human lung tumours. The functional significance of this Lmo2 expression was assessed in teratocarcinomas induced in nude mice by subcutaneous implantation of Lmo2-lacZ targeted ES cells. CD31-positive, sprouting endothelium of ES-cell origin occurred in teratocarcinomas from heterozygous Lmo2-lacZ ES cells but none occurred from null Lmo2-lacZ ES cells. Therefore, in this model Lmo2 is an obligatory regulator of neo-vascularization of tumours. These data suggest that LM02 function may be a drug target in cancer and other conditions characterized by neo-vascularization.

引用

页码：1309 / 1315

页数：7

共 23 条

[11] CHROMOSOMAL TRANSLOCATIONS IN HUMAN CANCER [J].

RABBITTS, TH .

NATURE, 1994, 372 (6502) :143-149

[12] Circulating endothelial precursors: mystery, reality, and promise [J].

Rafii, S .

JOURNAL OF CLINICAL INVESTIGATION, 2000, 105 (01) :17-19

[13] The scl gene product is required for the generation of all hematopoietic lineages in the adult mouse [J].

Robb, L ;

Elwood, NJ ;

Elefanty, AG ;

Kontgen, F ;

Li, RL ;

Barnett, LD ;

Begley, CG .

EMBO JOURNAL, 1996, 15 (16) :4123-4129

[14]

ROYERPOKORA B, 1991, ONCOGENE, V6, P1887

[15] THE LIM DOMAIN IS A MODULAR PROTEIN-BINDING INTERFACE [J].

SCHMEICHEL, KL ;

BECKERLE, MC .

CELL, 1994, 79 (02) :211-219

[16] Molecular and clinical differences between adenocarcinomas of the esophagus and of the gastric cardia [J].

Taniére, P ;

Martel-Planche, G ;

Maurici, D ;

Lombard-Bohas, C ;

Scoazec, JY ;

Montesano, R ;

Berger, F ;

Hainaut, P .

AMERICAN JOURNAL OF PATHOLOGY, 2001, 158 (01) :33-40

[17] THE LIM PROTEIN RBTN2 AND THE BASIC HELIX-LOOP-HELIX PROTEIN TAL1 ARE PRESENT IN A COMPLEX IN ERYTHROID-CELLS [J].

VALGEARCHER, VE ;

OSADA, H ;

WARREN, AJ ;

FORSTER, A ;

LI, J ;

BAER, R ;

RABBITTS, TH .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (18) :8617-8621

[18] Unsuspected role for the T-cell leukemia protein SCL/tal-1 in vascular development [J].

Visvader, JE ;

Fujiwara, Y ;

Orkin, SH .

GENES & DEVELOPMENT, 1998, 12 (04) :473-479

[19] SPECIFIC IN-VIVO ASSOCIATION BETWEEN THE BHLH AND LIM PROTEINS IMPLICATED IN HUMAN T-CELL LEUKEMIA [J].

WADMAN, I ;

LI, JX ;

BASH, RO ;

FORSTER, A ;

OSADA, H ;

RABBITTS, TH ;

BAER, R .

EMBO JOURNAL, 1994, 13 (20) :4831-4839

[20] THE ONCOGENIC CYSTEINE-RICH LIM DOMAIN PROTEIN RBTN2 IS ESSENTIAL FOR ERYTHROID DEVELOPMENT [J].

WARREN, AJ ;

COLLEDGE, WH ;

CARLTON, MBL ;

EVANS, MJ ;

SMITH, AJH ;

RABBITTS, TH .

CELL, 1994, 78 (01) :45-57

← 1 2 3 →