Yamada Yoshihiro, Pannell Richard, Forster Alan, Rabbitts Terence H
Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
Oncogene. 2002 Feb 21;21(9):1309-15. doi: 10.1038/sj.onc.1205285.
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 LMO2 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 LMO2 function may be a drug target in cancer and other conditions characterized by neo-vascularization.
实体瘤的生长需要通过对现有血管内皮进行重塑（血管生成）来提供血液供应。对于特异性控制肿瘤血管生成的转录调节因子，人们了解甚少。原癌基因LMO2编码一种含有LIM结构域的转录调节因子，该因子在小鼠胚胎发育过程中控制血管生成，在此过程中它调节毛细血管网络重塑为成熟血管。我们现在发现，Lmo2在肿瘤内皮细胞中表达增加，如小鼠胸腺瘤和人类肺癌。通过皮下植入Lmo2-lacZ靶向胚胎干细胞在裸鼠中诱导畸胎瘤，评估了这种Lmo2表达的功能意义。杂合Lmo2-lacZ胚胎干细胞来源的畸胎瘤中出现了CD31阳性、呈芽状的胚胎干细胞来源内皮细胞，但Lmo2基因敲除的Lmo2-lacZ胚胎干细胞来源的畸胎瘤中未出现。因此，在该模型中，Lmo2是肿瘤新生血管形成的必需调节因子。这些数据表明，LMO2的功能可能是癌症以及其他以新生血管形成为特征的疾病的药物靶点。
