Division of Biological Science and Research Center for Women's Diseases, Sookmyung Women's University, Seoul, Korea.
Oncol Rep. 2011 Jan;25(1):245-52.
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 I, 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.
ADCYAP1 基因编码一种腺苷酸环化酶激活多肽 1。ADCYAP1 已知参与多种生物过程。ADCYAP1 启动子区域存在多个胞嘧啶鸟嘌呤二核苷酸（CpG 岛）。启动子超甲基化导致转录沉默是许多癌症中肿瘤发生的重要调节机制。因此，研究了 8 种宫颈癌细胞系和具有不同恶性转化程度的人组织样本中 ADCYAP1 启动子的甲基化水平。虽然在 CIN III 和浸润性癌细胞以及 7 种宫颈癌细胞系中，ADCYAP1 启动子的多个 CpG 位点高度甲基化，但在正常细胞中很少甲基化。重要的是，ADCYAP1 启动子的甲基化似乎从 CIN I 开始，即多步骤致癌作用的相对早期阶段。这一事实表明，ADCYAP1 可以作为宫颈癌早期诊断的有效和敏感的甲基化生物标志物。此外，我们的数据表明，ADCYAP1 启动子高甲基化水平与宫颈癌的发展相关。我们还表明，在宫颈癌细胞中，5'-氮杂-2'-脱氧胞苷的 DNA 甲基转移酶抑制剂和/或曲古抑菌素 A 的组蛋白去乙酰化酶抑制剂的处理可以重新激活 ADCYAP1 基因的表达，表明 ADCYAP1 启动子的高甲基化导致了宫颈癌细胞中 ADCYAP1 基因的转录沉默。
