TSG101在肺癌组织和细胞系中的表达及意义  

Expression and its significance of TSG101 in lung cancer tissue and lung cancer cell lines

作　　者：蔡存伟[1] 张道荣[1] 陆平[2] 高艳华[1] 常家辉[1] 

机构地区：[1]中国医科大学基础医学院病理教研室,沈阳110001 [2]齐齐哈尔医学院附属五院大庆市龙南医院病理科,163453

出　　处：《中国肺癌杂志》2008年第2期172-177,共6页Chinese Journal of Lung Cancer

摘　　要：背景和目的在小鼠NIH3T3成纤维细胞中通过随机纯合子敲除法证实,破坏肿瘤易感基因TSG101(Tumor Susceptibility Gene101)导致裸鼠的自发性肺转移性肿瘤,从而TSG101作为侯选的肿瘤抑制基因被认识。随后,越来越多的研究证实TSG101并非是严格意义上的肿瘤抑制基因,在原发乳腺癌并没有检测到基因内部的序列的丢失或异常,相反发现存在异常的TSG101选择性剪接体。本研究目的旨在研究肺癌细胞系和组织中TSG101的表达情况,分析TSG101及异常的TSG101选择性剪接体在肺癌的发生发展过程中可能所起的作用。方法采用免疫组织化学方法(SP法)检测79例肺鳞癌和肺腺癌组织及相应癌旁正常肺组织中TSG101的表达情况。采用RT-PCR实验分析,检测出在7种肺癌细胞系中野生型和异常剪接转录产物表达情况。采用WesternBlot方法检测肺癌细胞系中蛋白质表达情况。结果TSG101在肺鳞癌和肺腺癌中的蛋白水平显著低于其在相应正常肺组织中的表达。七种细胞系中普遍存在由于异常的选择性剪接而缩短的TSG101转录产物,和野生性转录产物同时表达。通过统计学分析发现在小细胞肺癌细胞系中存在更多的异常的转录产物。通过WesternBlot分析同样发现小细胞肺癌细胞系同样与其他非小细胞肺癌细胞系在蛋白水平上存在差异。结论尽管在非小细胞肺癌中作为侯选的肿瘤抑制因子,但是普遍存在的TSG101异常转录产物也许和肺癌的类型相关,可作为肺癌恶性进展的生物学标志。Background and objective It has been proven that TSG101 is a candidate tumor suppressor gene whose deletion in NIH3T3 cells leads to spontaneous lung metastases in nude mice. Aberrant transcripts of TSG101 have been identified in primary breast carcinomas without evidence of intragenic deletions. To investigate the possible role of TSG101 and aberrant transcripts of TSC101 in lung cancer, we performed transcript analysis and protein analysis in lung cancer cell lines and lung cancer tissue. Methods Immunohistochemical method （S-P method） was used to detect the expression of T SG101 in 79 human squamous carcinoma and adenocarcinoma cases with the neighboring noncancerous tissue. RT-PCR was adopted to detect a common shortened TSG101 transcript because of aberrant alternative splicing and the wild-type transcript in lung cancer lines. Western Blot method was adopted to detect the expression of TSG101 protein in lung cell cells. Results The expression of TSG101 protein in tumor tissues was significantly lower than that in the neighboring noncancerous tissue. Reverse transcriptase RT-PCR analysis detected a common shortened TSG101 transcript because of aberrant alternative splicing, which was co-expressed with the wild-type transcript in seven lung cancer lines. Although shortened transcript was detected in all of lung cell cells being involved in our experiment, there is more aberrant transcipts in small cell lung cancer （SCLC） lines .Western blot analysis have detected the same differences in protein level. Conclusion TSC101 is a candidate tumor suppressor in non small cell lung cancer. However the common TSG101 aberrant transcript may be associated with types of lung cancer, and can be used as valuable biomarkers to evaluate lung cancer poor prognosis.

关 键 词：肺肿瘤 TSG101蛋白 选择性剪接体 

分 类 号：R734.2[医药卫生—肿瘤]