Department of Pharmaceutical Biochemistry, Poznań University of Medical Sciences, Poznań, Poland.
Toxicol In Vitro. 2011 Feb;25(1):213-21. doi: 10.1016/j.tiv.2010.11.003. Epub 2010 Nov 13.
Promoter hypermethylation is one of the mechanisms in the transcriptional inactivation of certain carcinoma - associated genes. In laryngeal cancers hypermethylation of tumor suppressor genes is related to their major risk factors- cigarette smoking and drinking strong alcohols. Since DNA methylation is reversible, modulation of the activity of DNA methyltransferases is an established therapeutic strategy, which can be also applied in cancer chemoprevention. Here, using the MSP procedure, we evaluated the frequency of hypermethylation of RARbeta, RASSF1A, HIN-1, GSTP1, MGMT, VHL and DAPK genes in several laryngeal and other head and neck squamous cell carcinoma cell lines and the effect of various polyphenols on the methylation of RARbeta and MGMT genes in the UT-SCC 42B cell line. Most of the cell lines tested were characterized by the hypermethylation of at least one of the genes analyzed. The most frequently hypermethylated genes were RARbeta and MGMT, while GSTP1 and VHL were not methylated in any of the cell lines. None of the tested compounds, including decitabine used as a reference compound, changed the methylation of RARbeta and MGMT genes. These findings suggest that although hypermethylation of RARbeta and MGMT may be considered as potential epigenetic biomarker, their application as therapeutic/chemopreventive targets requires further studies.
启动子甲基化是某些癌相关基因转录失活的机制之一。在喉癌中，肿瘤抑制基因的甲基化与主要的危险因素——吸烟和饮酒有关。由于 DNA 甲基化是可逆的，因此调节 DNA 甲基转移酶的活性是一种既定的治疗策略，也可以应用于癌症化学预防。在这里，我们使用 MSP 程序评估了 RARβ、RASSF1A、HIN-1、GSTP1、MGMT、VHL 和 DAPK 基因在几种喉癌和其他头颈部鳞状细胞癌细胞系中的超甲基化频率，以及各种多酚对 UT-SCC 42B 细胞系中 RARβ 和 MGMT 基因甲基化的影响。测试的大多数细胞系至少表现出分析的一个基因的超甲基化。最常超甲基化的基因是 RARβ 和 MGMT，而 GSTP1 和 VHL 在任何细胞系中都没有甲基化。包括作为参考化合物的地西他滨在内的测试化合物均未改变 RARβ 和 MGMT 基因的甲基化。这些发现表明，尽管 RARβ 和 MGMT 的超甲基化可以被认为是潜在的表观遗传生物标志物，但将其作为治疗/化学预防靶点的应用需要进一步研究。
