Department of Medical Oncology and Laboratory of Signal Transduction and Molecular Targeting Therapy, West China Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Division of Experimental Hematology and Cancer Biology, Children's Hospital Research Foundation, University of Cincinnati, Cincinnati, OH 45229, USA.
Int J Oncol. 2014 Mar;44(3):896-904. doi: 10.3892/ijo.2014.2245. Epub 2014 Jan 7.
Previous studies have shown that RhoE, an atypical member of the Rho GTPase family, may play an opposite role to RhoA in regulating cell proliferation and invasion. To explore the relationship between RhoE and the malignant phenotypes of human cancer, we have determined the expression patterns of RhoE in varying grade of human cancer tissues and tested the effects of RhoE expression in several RhoE underexpressing cancer cell lines. Systemic immunocytochemistry analyses of gastric, colorectal, lung and breast carcinomas, respectively, showed that RhoE protein expression was significantly decreased in most cancer cases compared with that of adjacent normal tissues. Enhanced RhoE expression could markedly inhibit proliferation, migration and invasion and induce apoptosis of the cancer cells which have relatively low levels of endogenous RhoE expression. Wild-type p53 (wt-p53) could strongly increase RhoE expression in p53-transfected cells. Furthermore, the luciferase assays indicated that wt-p53 significantly enhanced the activities of RhoE promoter compared with mutant p53 (mt-p53) in PC3 cells (p53 null). Collectively, data are presented showing that RhoE may participate in human cancer progression and act as a candidate target of p53, and these findings also strongly suggest that RhoE may be a new candidate tumor suppressor and could serve as a potential target in the gene therapy of cancer.
先前的研究表明，RhoE，Rho GTPase 家族中的一个非典型成员，可能在调节细胞增殖和侵袭方面发挥与 RhoA 相反的作用。为了探讨 RhoE 与人类癌症恶性表型之间的关系，我们测定了不同分级的人类癌症组织中 RhoE 的表达模式，并在几个 RhoE 低表达的癌细胞系中测试了 RhoE 表达的效应。对胃癌、结直肠癌、肺癌和乳腺癌的系统性免疫细胞化学分析分别表明，与相邻正常组织相比，RhoE 蛋白表达在大多数癌症病例中显著降低。增强 RhoE 表达可显著抑制增殖、迁移和侵袭，并诱导 RhoE 内源性表达水平相对较低的癌细胞凋亡。野生型 p53（wt-p53）可在 p53 转染的细胞中强烈增加 RhoE 表达。此外，荧光素酶检测表明，wt-p53 在 PC3 细胞（p53 缺失）中显著增强 RhoE 启动子的活性，而突变型 p53（mt-p53）则没有。总之，这些数据表明 RhoE 可能参与人类癌症的进展，并作为 p53 的候选靶标，这一发现还强烈表明 RhoE 可能是一种新的候选肿瘤抑制因子，并可作为癌症基因治疗的潜在靶标。
