Ras相关的C3肉毒素底物1蛋白在胃癌组织中的表达和分布以及与胃癌进展的关系

Biological significance of relationship between nuclear localization of Racl and progression of gastric carcinoma

目的观察胃癌组织中Ras相关的c3肉毒素底物1（Racl）蛋白的表达和分布，探讨Racl蛋白的定位与胃癌进展之间的关系。方法采用免疫组化染色法检测48例胃癌患者肿瘤组织和癌旁组织中Racl蛋白的表达和分布，采用实时荧光PCR法检测48例胃癌组织中T淋巴瘤侵袭转移诱导因子1（Tiaral）和RaclmRNA的表达水平。结果48例胃癌组织中，Racl蛋白阳性表达38例（79．2％），其中31例（64．6％）定位于细胞核。48例癌旁组织中，Racl蛋白阳性表达9例（18．8％），全部定位于细胞质。Racl蛋白在胃癌和癌旁组织中的阳性表达率差异有统计学意义（u=6．43，P〈0．01），Racl蛋白在胃癌和癌旁组织中的核定位率差异亦有统计学意义（χ2=45．795，P〈0．001）。实时荧光PCR检测结果显示，Racl蛋白核定位胃癌组织中Racl和Tiaml mRNA的阳性表达率和中位数均明显高于Racl蛋白非核定位组（均P〈0．05）。Racl蛋白的细胞核定位与胃癌的分化程度、T分期以及局部淋巴结转移相关。结论在多数胃癌组织中，Racl蛋白定位于细胞核，Racl蛋白的核定位可能是Tiaml／Racl信号通路异常活化的表现，也可能预示着胃癌侵袭能力的增强。

Objective To observe the subcellular localization of Racl and the expression of Tiaml and Racl in gastric carcinoma, in order to reveal the relationship between the distribution of Racl and progression of gastric carcinoma. Methods Both carcinoma and adjacent normal tissue of 48 patients with gastric carcinoma were studied in this study. Tissue distribution and expression of Racl and Tiaml were analyzed by immunohistochemistry and real-time polymerase chain reaction （PCR）. Results Compared with that of adjacent non-cancerous gastric mucosa, the expression of Racl in cancer tissues was significantly increased. The positive rate of Racl expression was 18.8% （9/48 cases） in adjacent non-neoplastic gastric and 79.2% （38/48 cases） in cancer tissues. The positive staining was mainly located in the cell nuclei （31 samples）. The real-time PCR results demonstrated that the expression levels of Tiaml and Racl mRNA in cancerous tissues with nuclear localization of Racl were evidently increased. Furthermore, nuclear localization of Racl was associated with tumor stage and metastasis. Conclusions The majority of gastric cancer tissues show nuclear dislocalization of Racl expression, which may be a sign of abnormal activation of Tiaml-Racl pathway. It may suggest enhanced invasion ability of the gastric carcinoma.