RARβ在宫颈癌及癌前病变中的表达调控和意义*

The Regulation of RARβ Expression and Its Significance in Cervical Cancer and Precancerous Diseases

  • 摘要: 目的:宫颈癌组织中的维甲酸受体β(retinoic acid rece ptor beta,RAR β)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RAR β 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RAR β mRNA 及蛋白质表达水平。结果:1)与宫颈炎相比,RAR β 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)RAR β 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,RAR β 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。

     

    Abstract: Objective:Previous reports have shown that the gene promoter region of retinoic acid receptor β (RAR β) is aberrantly methylated in cervical carcinoma, implying inhibition of gene transcription. The aim of this study was to investi-gate the association of RAR β gene expression at the mRNA and protein levels wi th cervical cancer development. Methods: We collected 37cases 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. Results: (1) The mRNA expression of RAR β in CIN and cervical cancer was markedly decreased compared to cervicitis wi th a statistically very significant difference, and no difference was found between the mRNA levels in CIN and cervical cancer. (2) RAR β protein was expressed at normal levels in cervici tis and partial ly lost in a few cases. Wi th 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 i ts precancerous lesions, RAR β expression was downregulated at the transcriptional level and essential ly lost at the protein level . RAR β 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 methylation of the RARβ gene and the establ ishment of a biomarker profi le for cervical cancer.

     

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