Pan Yanglin, Bi Feng, Liu Na, Xue Yan, Yao Xuebiao, Zheng Yi, Fan Daiming
Institute of Digestive Disease, Xi'jing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, PR China.
Biochem Biophys Res Commun. 2004 Mar 12;315(3):686-91. doi: 10.1016/j.bbrc.2004.01.108.
Rho GTPases were previously shown to have an important role in cancer development and progression, including cell transformation, proliferation, invasion, metastasis, and angiogenesis. However, there is still little information available on the clinical significance of Rho GTPases expression in human cancer specimens. In the present study, we systemically investigated the mRNA expression levels of seven main members RhoA, RhoB, RhoC, Rac1, Rac2, Rac3, and Cdc42 of Rho family using semi-quantitative reverse transcription-PCR in 53 patients with gastric carcinoma and 7 gastric cancer cell lines. The total and activities of RhoA, Rac1 and Cdc42 in 5 gastric cancer cell lines were also examined. The mean mRNA expression levels of RhoA and Rac1 in gastric cancer tissue specimens were significantly higher than those in the adjacent non-tumorous tissue specimens (p < 0.01). The higher expression of RhoA was significantly correlated with higher TNM stage (p < 0.05) as well as with pooly differentiated histological type (p < 0.05) of gastric carcinoma. The increased expression of Rac1 was related to higher TNM stages of gastric carcinoma (p < 0.05). The expression levels of mRNA, total protein and activities of RhoA and Rac1 in 7 gastric cancer cell lines were all higher than that in gastric mucosal epithelial cell line GES-1. These findings indicate that RhoA and Rac1 may play important roles in the carcinogenesis and progression of gastric carcinoma.
Rho GTP酶此前被证明在癌症发展和进程中发挥重要作用，包括细胞转化、增殖、侵袭、转移和血管生成。然而，关于Rho GTP酶在人类癌症标本中的表达的临床意义，目前仍知之甚少。在本研究中，我们使用半定量逆转录聚合酶链反应，系统地研究了53例胃癌患者和7种胃癌细胞系中Rho家族7个主要成员RhoA、RhoB、RhoC、Rac1、Rac2、Rac3和Cdc42的mRNA表达水平。我们还检测了5种胃癌细胞系中RhoA、Rac1和Cdc42的总量和活性。胃癌组织标本中RhoA和Rac1的平均mRNA表达水平显著高于相邻的非肿瘤组织标本（p < 0.01）。RhoA的高表达与胃癌较高的TNM分期（p < 0.05）以及低分化组织学类型（p < 0.05）显著相关。Rac1表达增加与胃癌较高的TNM分期有关（p < 0.05）。7种胃癌细胞系中RhoA和Rac1的mRNA、总蛋白表达水平及活性均高于胃黏膜上皮细胞系GES-1。这些发现表明，RhoA和Rac1可能在胃癌的发生和发展中发挥重要作用。
