摘要
背景与目的:云南锡矿工人肺癌发生率极高。已有研究表明,脆性组氨酸三联体基因(fragile histidine triad,FHIT)异常与肺癌的发生、发展密切相关。本研究旨在探讨云锡矿工肺癌中FHIT外显子3、4、5、8缺失及其蛋白表达异常。方法:采用聚合酶链反应(polymerase chain reaction,PCR)技术检测30例云锡矿工肺癌组织、云锡矿工肺癌细胞株YTMCC及22例其他地区非矿工肺癌组织中FHIT外显子3、4、5、8的缺失。用免疫组化法检测90例人肺癌组织FHIT蛋白表达,并对43例云锡矿粉诱发的不同阶段F344大鼠肺癌肺组织进行FHIT蛋白检测。结果:FHIT基因异常在YTMLC细胞表现为FHIT基因3和8两个外显子的缺失,而矿工和非矿工肺癌组织可出现3、4、5、8中1个或几个外显子的杂合性缺失,云锡矿工肺鳞癌中FHIT基因外显子缺失及蛋白失表达率分别为68.2%及70.6%,矿工肺鳞癌和腺癌、非矿工肺鳞癌和腺癌FHIT基因杂合性缺失与正常肺组织相比差异均有显著性(P<0.01)。矿粉诱发F344大鼠肺癌变早期即有FHIT的失表达,在8例鳞状上皮非典型增生、原位癌及早期肺鳞癌FHIT蛋白失表达率达100%。结论:在矿工及非矿工肺癌中,FHIT基因外显子缺失及其蛋白表达异常均常见。肺癌早期及癌前病变即有很高的FHIT失表达率,对FHIT检测分析有可能作为肺癌早期筛查的指标之一。
BACKGROUND ＆ OBJECTIVE. Yunnan tin miners have an extremely high incidence of lung cancer. Abnormality of the fragile histidine triad （FHIT） gene has been proved to closely relate to lung cancer development. This study was to explore the loss of exons 3,4,5 and 8 of FHIT gene and FHIT protein expression in Yunnan Tin miners with lung cancer. METHODS. The exons 3,4,5,and 8 of FHIT gene in lung cancer cell line YTMCC of a Yunnan Tin miner, and 30 specimens of lung cancer from Yunnan Tin miners in Gejiu district and 22 specimens of lung cancer from non-miners in other regions were detected by polymerase chain reaction （PCR）. The expression of FHIT protein in 90 specimens of human lung cancer and 43 specimens of lung cancer developed by the intratracheal instillation of Yunnan Tin mineral dust in F344 rats was detected by immunohistochemistry. RESULTS： Losses of exon 3 and exon 8 were detected in YTMCC cells. Lung cancer samples from Yunnan Tin miners and non-miners exhibited heterozygous loss of FHIT gene among exons 3,4,5 and 8. The percentages of FHIT gene deletion and loss of FHIT protein expression in Yunnan Tin miners with lung cancer were 68.2% and 70.6%, respectively. The percentages of FHIT gene heterozygous loss was significantly higher in lung cancer tissue than in normal lung tissue （P〈0.01）. Loss of FHIT protein expression was detected in the early stage of F344 rat lung canceration after treatment of Yunnan tin Mineral dust.the percentage was 100% in 8 specimens of squamous dysplasia, carcinoma in situ, and early stage of squamous cell carcinoma. CONCLUSIONS： Deletion and abnormal expression of FHIT gene are common in Yunnan tin miners and non-miners with lung cancer. The high rate of loss of FHIT expression in precancerous lesions and lung cancer at early stage indicates that FHIT could be an early screening target of lung cancer.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2007年第6期607-612,共6页
Chinese Journal of Cancer
基金
国家自然科学基金项目(No.30160031)
云南省教育厅科学研究基金项目(No.06Z066C)~~
