LATS1在食管鳞癌中的表达及启动子甲基化状态研究

Expression and Promoter Methylation Status of LATS1 in Esophageal Squamous Cell Carcinoma

在我们以前的研究中,在食管鳞癌细胞株中过表达大肿瘤抑制基因-1（large tumor suppressor kinase 1,LATS1）能够明显抑制细胞增殖、细胞迁移和侵袭,同时能够促进细胞凋亡。为了进一步研究LATS1基因在食管鳞状细胞癌发生发展中的作用以及可能的机制,我们在食管鳞癌组织与配对癌旁组织中,应用免疫组化检测LATS1基因蛋白质表达情况,应用荧光定量PCR（qRT-PCR）检测配对组织LATS1基因mRNA表达差异。甲基化特异性PCR（MSP）和亚硫酸氢盐测序法（BGS）检测食管鳞癌组织及细胞中LATS1基因的CpG岛甲基化状态。我们发现LATS1基因在癌旁组织中广泛表达,而癌组织中LATS1基因表达明显下调。结果表明LATS1在食管鳞癌中起到抑癌基因的作用,并且与肿瘤的临床分期相关,而其下调与CpG岛的高甲基化无关。在食管鳞癌细胞中过表达LATS1抑制细胞增殖、细胞迁移和侵袭,同时能够促进细胞凋亡。因此,LATS1基因值得进一步探索作为食管鳞癌生物标志物的可能用途和未来分子诊断和治疗的目标。

In our previous res earch, ex ogenous expression of LATS1 in esophageal squamous cell carcinoma（ESCC） cells obviously inhibited cell proliferation, cell migration, cell invasion and promoted cell apoptosis. To investigate how LATS1 affects the progression of ESCC and its probable mechanisms, LATS1 expression in ESCC was dectected by quantitative reverse transcription polymerase chain reaction（q RT-PCR） and immunohisotochemical staining. Moreover, methylation status of LATS1 CpG islands in ESCC tissues and celss was detected by MSP and BGS. We found that LATS1 is widely expressed in adjacent normal esophageal tissues and inhibited in ESCC tissues. In summary, it was strongly indicated that LATS1 is a tumor suppressor gene in ESCC and is associated wi th the clinical stage of the tumor while its downregulation has no connection with the hypermethylation of CpG islands.Exogenous expression of LATS1 in ESCC cells obviously inhibited cell proliferation, cell migration, cell invasion and induced cell apoptosis. Thus, it would be of benefit to further explore the possible uses of LATS1 as a biomarker and a target for future molecular therapy and diagnosis.