Department of Ophthalmology & Visual Sciences and Siteman Cancer Center, Washington University School of Medicine, Campus Box 8096, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Clin Exp Metastasis. 2010 Feb;27(2):91-6. doi: 10.1007/s10585-010-9304-5. Epub 2010 Feb 2.
The inhibitor of DNA binding 2 (Id2) basic helix-loop-helix protein interacts genetically and physically with the pocket proteins (Rb, p107 and p130) and has been implicated as an oncogene. In other studies, however, Id2 has been shown to function as a tumor suppressor. Here, we studied the role of Id2 in a well characterized model of ocular cancer in which the three pocket proteins are inactivated by generating mice lacking one or both Id2 alleles. Id2 deficiency had no impact on tumorigenesis in the eye. Unexpectedly, however, Id2 loss significantly increased the rate of metastasis. Liver metastases in Id2 heterozygotes demonstrated significant decrease of Id2 expression and loss of the remaining Id2 allele, strongly suggesting that Id2 inactivation specifically was required for metastasis in this model. These findings provide new insights into the role of Id2 in metastasis.
DNA 结合抑制因子 2（Id2）碱性螺旋-环-螺旋蛋白与口袋蛋白（Rb、p107 和 p130）在遗传和物理上相互作用，被认为是一种癌基因。然而，在其他研究中，Id2 被证明具有肿瘤抑制因子的功能。在这里，我们研究了 Id2 在一种经过充分表征的眼部癌症模型中的作用，在该模型中，通过生成缺失一个或两个 Id2 等位基因的小鼠，使三个口袋蛋白失活。Id2 缺失对眼部肿瘤发生没有影响。然而，出人意料的是，Id2 缺失显著增加了转移的速度。Id2 杂合子的肝转移显示出 Id2 表达的显著下降和剩余 Id2 等位基因的丢失，这强烈表明在这种模型中，Id2 失活是转移所必需的。这些发现为 Id2 在转移中的作用提供了新的见解。
