SHEEC食管癌细胞中NGAL基因的功能  

Functions of Neutrophil Gelatinase-associated Lipocalin in the Esophageal Carcinoma Cell Line SHEEC

作　　者：李恩民[1] 许丽艳[2] 蔡唯佳 熊华淇 沈忠英 曾毅[3] 

机构地区：[1]汕头大学医学院生物化学与分子生物学教研室,汕头515031 [2]汕头大学医学院肿瘤病理研究室,汕头515031 [3]中国预防医学科学院病毒学研究所,北京100052

出　　处：《生物化学与生物物理学报》2003年第3期247-254,共8页

基　　金：国家自然科学基金 (No .3990 0 0 69和No .30 170 42 8);广东省自然科学基金 (No .0 10 431);广东省高校自然科学研究基金 (No .2 0 0 0 33);广东省医学科研基金 (No .A2 0 0 14 19);汕头大学研究与发展基金(No.L0 0 0 4)资助项目~~

摘　　要：中性粒细胞明胶酶相关脂质运载蛋白 (neutrophilgelatinase associatedlipocalin ,NGAL)是脂质运载蛋白(lipocalin)家族的一个新成员 ,可能是人类的一种新的癌基因 ,但是在肿瘤中的功能不清楚。以往研究发现NGAL基因在SHEEC食管癌细胞中显著过表达 ,表明该细胞是一种用来揭示NGAL基因在肿瘤中功能的良好模型。采用反义封闭技术 ,同时结合裸鼠成瘤实验等研究了反义封闭NGAL基因转录对SHEEC食管癌细胞的浸润和分裂增殖等行为的影响。结果发现 ,反义封闭NGAL基因转录不但可以有效地降低SHEEC细胞分泌的基质金属蛋白酶 9和基质金属蛋白酶 2的活性 ,而与此同时裸鼠成瘤细胞的浸润行为也相应地受到了明显抑制 ,然而SHEEC细胞端粒的长度、拓扑异构酶II的含量以及细胞增殖指数等未发生明显变化。表明NGAL基因在食管癌细胞SHEEC中的功能可能主要是通过明胶酶在促进肿瘤细胞的浸润中发挥作用 。Neutrophil gelatinase-associated lipocalin (NGAL) is a novel member of the lipocalin family and may be a new human oncogene product, but function of NGAL is not clear in the cancer. It was recently found that NGAL was overexpressed in the progression of malignant transformation from human immortalized esophageal epithelial cell line SHEE to esophageal carcinoma cell line SHEEC. This indicated that cell line SHEEC was a good model for exploring functions of NGAL in the carcinogenesis. The effects of blocking transcription of NGAL gene on invasion, division and proliferation of SHEEC cells were studied by antisense blocking RNA technique and tumor formation in nude mice. The results showed that the antisense blocking of transcription of NGAL gene not only decreased effectively the activity of MMP-9 and MMP-2 secreted by SHEEC cells, but suppressed significantly also the invasion of these cells in nude mice. However, the telomere length, the content of the cellular topoisomeraseⅡ-α and cellular proliferation index (PI) of the SHEEC cells have not been changed markedly. These results indicate that NGAL is possibly involved in invasion of tumor cells by regulating activity of MMP-9 and MMP-2, but is not apparently related with division and proliferation of tumor cells in SHEEC.

关 键 词：SHEEC食管癌细胞 NGAL基因 功能 肿瘤细胞浸润 明胶酶 裸鼠成瘤实验 

分 类 号：R735.1[医药卫生—肿瘤]