KAI-1转移抑制基因在裸鼠肾癌转移中的意义

The Significance of KAI-1 Tumor Metastasis Suppression Gene Expression for the Metastasis of Renal Carcinoma

目的通过临床回顾性分析发现T1-3aN0M0肾癌术后转移的发生与KAI-1表达缺失密切相关,提示KAI-1基因缺失可能参与了T1-3aN0M0肾癌术后转移。本研究拟运用动物实验进一步验证KAI-1在抑制肾癌转移方面的作用。方法选择1例肾癌KAI-1表达阴性标本,制成肾癌细胞悬液并传代培养。通过KAI-1质粒转染阴性肾癌细胞成KAI-1阳性肾癌细胞。分别用KAI-1阳性和阴性肾癌细胞各接种40只裸鼠,观察计算皮下成瘤生长情况和肺脏表面转移瘤数量。采用χ~2检验比较转移瘤数量差异。应用免疫组织化学和PCR方法检测KAI-1表达。结果所有裸鼠接种成瘤顺利,肿瘤增长迅速,接种后2～3周最为明显。40只KAI-1表达阳性裸鼠肺脏表面可见直径1～2mm灰红色米粒状结节,数量0～11个,平均6个。40只KAI-1表达阴性裸鼠肺脏表面结节数量0～57个,平均31个,数量比较χ~2=5.01,P〈0.05。结论 KAI-1表达缺失促进了肾癌细胞的转移,为临床检测KAI-1表达预测肾癌转移提供了可靠的实验证据。

Objective To test the statistical relationship between the loss of expression of KAI-1 on T1-3aN0M0 stage renal carcinoma specimens and the postoperative metastases. It implied that the loss of KAI-1 expression took part in the postoperative metastases of renal carcinoma. The study is to test testify the effect of KAI-1 to inhibit of renal carcinoma metastases by means of naked mice experiment. Methods A piece of KAI-1 negative specimen of renal carcinoma was chosen and was made to renal carcinoma cell solution and then these cell were incubated and stored. The KAI-1 negative renal carcinoma cells were transinfected into KAI-1 positive cells with KAI-1 gene plasmid. Every forty naked mice were inoculated with KAI-1 negative or positive renal carcinoma cell. The growth of subcutaneous tumor and the number of lung metastatic tumors in naked mice were counted and the results were compared by χ~2 testing. KAI-1 expression was examined with PCR and immunohistochemistry. Results Renal carcinoma cells were inoculated successfully in every naked mouse and tumor growth was observed and the tumors grew rapid dramatically from the second week to the third. There were 40 naked mice on which surface of lungs the grey and red nodules of 1～2mm in diameter were distinguished and the average number was 6 on surface of lung in each mouse with KAI-1 positive renal carcinoma（0～11）. Otherwise,the average number was 31 in KAI-1 negative mice（0～57）.There was statistical significant difference between the two groups（χ~2=5.01,P0.05）. Conclusion The loss of KAI-1 expression is able to promote the metastases of renal carcinoma. This kind of experimental evidence may help to prognosticate the clinical metastases of renal carcinoma by way of testing KAI-1 expression.