Durkin Marian E, Yuan Bao-Zhu, Zhou Xiaoling, Zimonjic Drazen B, Lowy Douglas R, Thorgeirsson Snorri S, Popescu Nicholas C
Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
J Cell Mol Med. 2007 Sep-Oct;11(5):1185-207. doi: 10.1111/j.1582-4934.2007.00098.x.
The deleted in liver cancer 1 (DLC-1) gene encodes a GTPase activating protein that acts as a negative regulator of the Rho family of small GTPases. Rho proteins transduce signals that influence cell morphology and physiology, and their aberrant up-regulation is a key factor in the neoplastic process, including metastasis. Since its discovery, compelling evidence has accumulated that demonstrates a role for DLC-1 as a bona fide tumour suppressor gene in different types of human cancer. Loss of DLC-1 expression mediated by genetic and epigenetic mechanisms has been associated with the development of many human cancers, and restoration of DLC-1 expression inhibited the growth of tumour cells in vivo and in vitro. Two closely related genes, DLC-2 and DLC-3, may also be tumour suppressors. This review presents the current status of progress in understanding the biological functions of DLC-1 and its relatives and their roles in neoplasia.
肝癌缺失基因1(DLC-1)编码一种GTP酶激活蛋白,该蛋白作为小GTP酶Rho家族的负调控因子发挥作用。Rho蛋白转导影响细胞形态和生理功能的信号,其异常上调是肿瘤形成过程(包括转移)中的关键因素。自发现以来,越来越多的确凿证据表明DLC-1在不同类型的人类癌症中作为一种真正的肿瘤抑制基因发挥作用。由遗传和表观遗传机制介导的DLC-1表达缺失与许多人类癌症的发生发展相关,而DLC-1表达的恢复在体内和体外均抑制肿瘤细胞的生长。另外两个密切相关的基因,DLC-2和DLC-3,也可能是肿瘤抑制基因。本文综述了目前在理解DLC-1及其相关基因的生物学功能及其在肿瘤形成中的作用方面的研究进展。