Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
Ann Surg Oncol. 2012 Jan;19(1):145-53. doi: 10.1245/s10434-011-1944-4. Epub 2011 Aug 23.
RhoGDI2 has been identified as a regulator of tumor metastasis but its role in cancer remains controversial. The aims of this study were to analyze the function of RhoGDI2 in colorectal carcinoma (CRC), and to determine its possible signaling pathway in CRC.
The expression of RhoGDI2 was detected in CRC cell lines, and 20 matched pairs of fresh CRC tissues, and 120 cases of clinical paraffin-embedded CRC tissues by real-time RT-PCR, Western blot, RT-PCR, or immunohistochemistry. The levels of activations of p-PI3K, p-Akt, p-MAPK, and p-MEK were then examined in RhoGDI2-overexpressing cells by Western blot. A series of assays were finally performed to evaluate the effect of RhoGDI2 on CRC cell behaviors in vitro.
RhoGDI2 expression was higher in highly metastatic CRC cell lines than in lowly metastatic ones. RhoGDI2 expression was up-regulated in CRC or lymphatic metastatic tissues relative to normal mucosa (P < 0.05). RhoGDI2 expression was correlated strongly with tumor size, differentiation, and Duke's stage (P < 0.05). Patients with lower RhoGDI2 expression had better overall survival (P = 0.012), and RhoGDI2 could predict prognosis only in patients with early-stage disease. High levels of activations of p-PI3K and p-Akt were observed in RhoGDI2-overexpressing cells. LY294002 inhibitor could abrogate the activation of PI3K/Akt pathway in those cells. Over-expression of RhoGDI2 enhanced CRC cell proliferation, motility, and invasion in vitro.
Over-expression of RhoGDI2 is associated with poor overall survival in CRC patients, especially those presenting in early-stage. RhoGDI2 contributes to cell proliferation, motility, and invasion of CRC, at least in part, by activating the PI3K/Akt pathway.
RhoGDI2 已被鉴定为肿瘤转移的调节剂，但它在癌症中的作用仍存在争议。本研究旨在分析 RhoGDI2 在结直肠癌（CRC）中的功能，并确定其在 CRC 中的可能信号通路。
通过实时 RT-PCR、Western blot、RT-PCR 或免疫组织化学检测 RhoGDI2 在 CRC 细胞系、20 对新鲜 CRC 组织和 120 例临床石蜡包埋 CRC 组织中的表达。然后通过 Western blot 检测 RhoGDI2 过表达细胞中 p-PI3K、p-Akt、p-MAPK 和 p-MEK 的激活水平。最后进行了一系列实验来评估 RhoGDI2 对 CRC 细胞体外行为的影响。
高度转移性 CRC 细胞系中 RhoGDI2 的表达高于低度转移性细胞系。CRC 或淋巴转移组织中 RhoGDI2 的表达高于正常黏膜（P<0.05）。RhoGDI2 的表达与肿瘤大小、分化和 Duke 分期密切相关（P<0.05）。RhoGDI2 表达较低的患者总生存期较好（P=0.012），RhoGDI2 仅在早期疾病患者中可预测预后。RhoGDI2 过表达细胞中观察到 p-PI3K 和 p-Akt 的激活水平升高。LY294002 抑制剂可阻断这些细胞中 PI3K/Akt 通路的激活。RhoGDI2 的过表达增强了 CRC 细胞在体外的增殖、迁移和侵袭能力。
RhoGDI2 的过表达与 CRC 患者的总生存期较差相关，尤其是早期患者。RhoGDI2 通过激活 PI3K/Akt 通路促进 CRC 细胞的增殖、迁移和侵袭。
