摘要
目的:宫颈癌组织中的维甲酸受体β(retinoic acid receptor beta,RARβ)基因启动子区发生异常甲基化,一般提示其抑制基因的转录表达。本研究从mRNA和蛋白质水平观察宫颈癌发生与RARβ表达调控的关系和意义。方法:选择妇女宫颈炎、宫颈内上皮瘤样病变(cervical intraepithelial neoplasia,CIN)和宫颈鳞癌患者,收集新鲜组织标本37例及石蜡包埋组织126例,采用定量RT-PCR及免疫组织化学方法鉴定RARβmRNA及蛋白质表达水平。结果:1)与宫颈炎相比,RARB基因在CIN和宫颈癌组织中的mRNA表达水平明显下降,但是CIN与宫颈癌之间没有统计学差异(P>0.05)。2)RARβ蛋白在宫颈上皮细胞核正常表达,少数病例出现"部分缺失"(8%),但是随着CIN和宫颈癌发病进程,不仅发生"完全缺失",而且其缺失频率逐渐增高(38%和57%),与宫颈炎比较有显著差异(P<0.01)。结论:在宫颈癌及癌前病变组织中,RARβ转录水平表达下调及蛋白质水平表达出现缺失,可能是肿瘤发生的重要标志。本结果为进一步研究该基因异常甲基化相关的机制,并建立宫颈癌的生物标志物体系提供了客观依据。
Objective： Previous reports have shown that the gene promoter region of retinoic acid receptor β （RARβ） is aberrantly methylated in cervical carcinoma, implying inhibition of gene transcription. The aim of this study was to investi- gate the association of RARβ gene expression at the mRNA and protein levels with cervical cancer development. Methods： We collected 37 cases of fresh cervical tissues and 126 cases of formalin fixed and paraffin embedded cervical tissue spec- imens from women with cervicitis, cervical intraepithelial neoplasia （CIN） and cervical squamous cell carcinoma. Quantita- tive RT-PCR was used to detect mRNA expression and immunohistochemistry was used to assess protein expression. Resuits： （1） The mRNA expression of RARβ in CIN and cervical cancer was markedly decreased compared to cervicitis with a statistically very significant difference, and no difference was found between the mRNA levels in CIN and cervical cancer. （2） RARβ protein was expressed at normal levels in cervicitis and partially lost in a few cases. With the development of CIN and cervical cancer, a significant loss of protein expression occurred that gradually increased （38% and 57%） and was very different from the level found in cervicitis （P〈0.01）. Conclusion： In cervical cancer and its precancerous lesions, RARβ expression was downregulated at the transcriptional level and essentially lost at the protein level. RARβ expression may be an important marker of cancer development. The results shown here may provide evidence for further study of the mecha- nism related to aberrant methylaUon of the RARβ gene and the establishment of a biomarker profile for cervical cancer.
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2010年第20期1157-1160,共4页
Chinese Journal of Clinical Oncology
基金
国家自然科学基金(编号:30760279)
新疆高校科研计划基金资助(编号:XJEDU2007125)~~
