癌基因Gli2促进肾癌细胞的体外侵袭能力

目的:研究Gli2与肾癌细胞侵袭之间的关系。方法:采用免疫组织化学染色的方法对41例肾癌临床标本中Gli2的表达情况进行检测，并分析Gli2在局部侵袭性肾癌和非局部侵袭性肾癌中的表达差异。运用肾癌细胞模型，通过过表达Gli2质粒或添加Gli2特异性抑制剂干预细胞，采用体外侵袭实验分析Gli2在肾癌细胞侵袭能力中的作用，RT-PCR检测Gli2对细胞侵袭相关基因的调控作用。结果:Gli2蛋白在T3-4期肾癌中的表达水平明显高于T1-2期（P＜0.05），Gli2过表达能明显促进肾癌细胞的体外侵袭能力，反之，Gli2特异性的抑制剂Gant61则显著减弱肾癌细胞的体外侵袭能力。Gli2抑制肾癌细胞上皮标记物E-Cadherin的表达，上调间质标记物N-Cadherin，Vimentin，MMP-2及MMP-9的表达；Gli2抑制剂的作用则相反。结论:Gli2通过调控侵袭相关基因的表达促进肾癌细胞的侵袭。

The oncogene Gli2 promotes in vitro cell invasion of renal cell carcinoma

Objective:Our previous studies demonstrated that Gli2 played crucial roles in the tumorigenesis, growth and resistance to radiotherapy of renal cell carcinoma(RCC),the present study is aimed to further investigate the biological function of Gli2 in RCC cell invasion. Methods:Immunohistochemical staining was performed to deter-mine the expression of Gli2 in 41 RCC clinical specimens,and the difference of Gli2 levels in local non - invasive and local invasive RCC was analyzed. Further RCC cell lines was either transfected with Gli2 - overexpression plasmid or Gli2 specific inhibitor Gant61,then in vitro Transwell assays were performed to determine the effect of Gli2 on RCC cell invasion and RT - PCR was performed to analyze the expression invasion - related genes. Results:Gli2 was highly expressed in stage T3 - 4 RCC tumors which were local invasive compared to T1 - 2 RCC tumors which were local non -invasive tumors(P < 0. 05). Cell line model based in vitro assays demonstrated that overexpression of Gli2 promoted RCC cell invasion,whereas,Gli2 inhibitor Gant61 suppressed cell invasion. Additionally,Gli2 downregulated epithelial marker E - Cadherin and upregulated mesenchymal markers N - Cadherin,Vimentin,MMP - 2 and MMP - 9,howev-er,Gant61 exhibited the opposite effects. Conclusion:Gli2 could promote RCC cell invasion via regulation of some cancer cell invasion related genes.