抑癌基因DCC在肺癌中的表达及杂合性丢失

Expression and losa of heterozygosity of DCC gene inhuman lung cancer

为探讨结肠癌缺失基因（ＤＣＣ）与肺癌发病的关系，利用半定量的逆转录聚合酶链反应（ＲＴ－ＰＣＲ）结合Ｓｏｕｔｈｅｒｎ杂交分析了７例肺癌患者（４例鳞癌和３例腺癌）癌组织及正常肺组织中ＤＣＣ基因ｍＲＮＡ的表达，发现４例肿瘤组织中ＤＣＣ基因表达明显低于对照肺组织。７例标本分析结果表明肺癌组织中ＤＣＣ基因的表达水平为正常肺组织的４５％左右。对上述７例及另外８例标本的两个多态位点进行ＰＣＲ杂合性丢失（ＬＯＨ）分析，信息性个体占９例，其中５例表现杂合性丢失：２例在ＭｓｐＩ限制性长度多态片段（ＲＦＬＦ），３例为可变数量串连重复序列（ＶＮＴＲ）。本结果证明在肺癌组织中存在ＤＣＣ基因表达低下及ＬＯＨ改变，提示其可能为肺癌发病的易感基因之一。

he level of DCC mRNA expression was evaluatedin tissue specimens from lung cancer patients by semi-quantitative reverse transcription-polymerase chain reac-tion (RT-PCR) combined with Southern blot analysis.Obvious reduction of DCC gene expression was observedin 4 of 7 specimens (55%). In two specimens DCCtranscript could only be detected after Southern blot hy-bridization of RT-PCR product. The average level ofDCC expression in cancer tissue was about 45% of nor-mal tissue as estimated by laser densitometer. We alsostudied DNA samples for loss of heterozygosity (LOH)at DCC locus at two polymorphic sites. Among the 15specimens including 7 samples for RT-PCR, 9 (60%)were informative at either of two polymorphic sites.LOH was observed in 5 (55%). Two at the MspI-RFLP (rrestriction fragment length polymorphism) siteand 3 at the site of VNTR (variable number of tandemrepeat). These results suggest that allele loss and de-creased expression of DCC gene are frequent events andthe possible involvement of DCC gene in the pathogene-sis of human lung cancer.