Department of Medical Oncology and Laboratory of Signal Transduction and Molecular Targeting Therapy, The State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People's Republic of China.
Int J Cancer. 2011 Mar 1;128(5):1057-68. doi: 10.1002/ijc.25445.
Although Rho family GTPases RhoA, RhoB and RhoC share more than 85% amino acid sequence identity, they may play distinct roles in tumor progression. RhoA and RhoC have been suggested to have positive effects on tumor progression, but the role of RhoB in cancer, particularly in gastric cancer, remains unclear. In our study, we have examined the expression levels of these three Rho GTPases in a large panel of specimens from gastric cancer patients by immunohistochemistry. We found that RhoA and RhoC expression were significantly elevated, while RhoB was reduced or absent, in surgically removed gastric cancer tissues when compared to normal gastric tissues. The significant reduction of RhoB expression was confirmed in another group of gastric cancer samples in comparison to the adjacent non-neoplastic tissues. Then we transfected the plasmids containing RhoA, RhoB or RhoC cDNA into two gastric cancer cell lines, SGC7901 and AGS cells, respectively. By overexpression experiments, we found that RhoA promoted the gastric cancer cell proliferation and RhoC stimulated migration and invasion of the cancer cell. RhoB expression, however, significantly inhibited the proliferation, migration and invasion of the gastric cancer cells and also enhanced the chemosensitivity of these cells to anticancer drugs. It appears that RhoB plays an opposing role from that of RhoA and/or RhoC in gastric cancer cells. Our work suggests that RhoB may play a tumor suppressor role and subsequently may have potential implications in future targeted therapy.
虽然 Rho 家族 GTP 酶 RhoA、RhoB 和 RhoC 具有超过 85%的氨基酸序列同一性，但它们在肿瘤进展中可能发挥不同的作用。RhoA 和 RhoC 被认为对肿瘤进展有积极影响，但 RhoB 在癌症中的作用，特别是在胃癌中的作用尚不清楚。在我们的研究中，我们通过免疫组织化学检测了大量胃癌患者标本中这三种 Rho GTP 酶的表达水平。我们发现，与正常胃组织相比，手术切除的胃癌组织中 RhoA 和 RhoC 的表达显著升高，而 RhoB 的表达则降低或缺失。在另一组胃癌样本与相邻非肿瘤组织的比较中，证实了 RhoB 表达的显著减少。然后，我们将含有 RhoA、RhoB 或 RhoC cDNA 的质粒分别转染到两种胃癌细胞系 SGC7901 和 AGS 细胞中。通过过表达实验，我们发现 RhoA 促进胃癌细胞增殖，而 RhoC 刺激癌细胞迁移和侵袭。然而，RhoB 的表达显著抑制了胃癌细胞的增殖、迁移和侵袭，并增强了这些细胞对抗癌药物的化疗敏感性。RhoB 在胃癌细胞中似乎发挥着与 RhoA 和/或 RhoC 相反的作用。我们的工作表明，RhoB 可能发挥肿瘤抑制作用，随后可能对未来的靶向治疗具有潜在意义。
