The role of ADCYAP1, adenylate cyclase activating polypeptide 1, as a methylation biomarker for the early detection of cervical cancer
The role of ADCYAP1, adenylate cyclase activating polypeptide 1, as a methylation biomarker for the early detection of cervical cancer
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DOI：
10.3892/or_00001067
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发表时间：
2011-01-01
期刊：
影响因子：
4.2
通讯作者：
Lee, Myeong-Sok
中科院分区：
文献类型：
--
作者：
Jung, Samil;Yi, Lisha;Lee, Myeong-Sok
ADCYAP 1基因编码腺苷酸环化酶激活多肽1。已知ADCYAP 1参与多种生物过程。在ADCYAP 1启动子区发现多个胞嘧啶鸟嘌呤二核苷酸（CpG岛）。启动子甲基化导致的转录沉默是许多癌症发生的重要调控机制。因此，ADCYAP 1启动子的甲基化水平进行了研究，在8个宫颈癌细胞系和人类组织样本具有不同程度的恶性转化。虽然ADCYAP 1启动子中的多个CpG位点在CIN III和浸润性癌细胞以及7种宫颈癌细胞系中高度甲基化，但它们在正常细胞中很少甲基化。重要的是，ADCYAP 1启动子的甲基化似乎从CIN 1开始，这是多步癌变的相对早期阶段。这一事实表明，ADCYAP 1可以作为一个有效的和敏感的甲基化生物标志物，用于宫颈癌的早期诊断。此外，我们的数据表明，ADCYAP 1启动子高甲基化水平与宫颈癌的发展相关。我们还表明，ADCYAP 1基因的表达被重新激活的DNA甲基转移酶抑制剂的5 '-氮杂-2'-脱氧胞苷和/或组蛋白脱乙酰酶抑制剂的宫颈癌细胞中，表明在ADCYAP 1启动子的超甲基化是负责的ADCYAP 1基因在宫颈癌细胞中的转录沉默。
The ADCYAP1 gene encodes an adenylate cyclase activating polypeptide 1. ADCYAP1 has been known to be involved in various biological processes. Multiple cytosine guanine dinucleotides (CpG island) are found in the ADCYAP1 promoter region. Transcriptional silencing by promoter hypermethylation is an important regulatory mechanism in tumorigenesis in many cancers. Therefore, the methylation level of the ADCYAP1 promoter was investigated in eight cervical cancer cell lines and human tissue samples with a distinctive degree of malignant transformation. While multiple CpG sites in the ADCYAP1 promoter were highly methylated in CIN III and invasive carcinoma cells as well as seven cervical cancer cell lines, they were rarely methylated in normal cells. Importantly, methylation in the ADCYAP1 promoter seems to start from CIN 1, relatively early stage of multistep carcinogenesis. This fact suggest that ADCYAP1 can be used as an effective and sensitive methylation biomarker for the early diagnosis of cervical cancer. Moreover, our data imply that the level of the ADCYAP1 promoter hypermethylation is correlated with cervical cancer development. We also show that ADCYAP1 gene expression was reactivated by the treatment of a DNA methyltransferase inhibitor of 5'-aza-2'deoxycytidine and/or a histone deacetylase inhibitor of trichostain A in cervical cancer cells suggesting that hypermethylation in the ADCYAP1 promoter is responsible for the transcriptional silencing of the ADCYAP1 gene in cervical cancer cells.