Oikonomou Pagona, Messinis Ioannis, Tsezou Aspasia
Department of Biology, Medical School, University of Thessalia, Larisa, Greece.
Exp Biol Med (Maywood). 2007 Jul;232(7):881-6.
Human telomerase reverse transcriptase (hTERT) mRNA expression seems to play an important role in cervical carcinogenesis. Analysis of the hTERT promoter region revealed the presence of a CpG island and a high overall GC content, suggesting a possible role for methylation in the regulation of hTERT gene expression. The present study was designed to evaluate the role of hTERT promoter methylation and E6/E7 human papilloma virus 16 (HPV-16) mRNA expression in hTERT regulation in premalignant cervical specimens. The methylation status of the hTERT promoter gene and hTERT mRNA quantification were investigated in 26 normal and 64 specimens of abnormal cytology using the MethyLight technique, Telo-TAGGG hTERT Quantification Kit and LightCycler technology. E6/E7 HPV-16 mRNA expression was also evaluated. No significant correlations were observed between hTERT mRNA expression and hTERT promoter methylation, as well as between telomerase activity and hTERT promoter methylation in normal and in premalignant cervical specimens. E6/E7 HPV-16 mRNA expression was observed in 72% of HPV-16-infected samples and was correlated with hTERT mRNA expression and telomerase activity (P < 0.05). This is the first study investigating the role of hTERT promoter methylation in hTERT mRNA expression and telomerase activity in premalignant lesions. The observed lack of correlation suggests that other mechanisms might be involved in the regulation of hTERT expression. The correlation between hTERT mRNA and E6/E7 mRNA expression confirms the role of HPV infection in hTERT regulation.
人端粒酶逆转录酶（hTERT）mRNA表达似乎在宫颈癌发生过程中发挥重要作用。对hTERT启动子区域的分析显示存在一个CpG岛且总体GC含量较高，提示甲基化可能在hTERT基因表达调控中发挥作用。本研究旨在评估hTERT启动子甲基化和人乳头瘤病毒16型（HPV - 16）E6/E7 mRNA表达在宫颈癌前病变标本中对hTERT调控的作用。使用甲基化荧光定量技术、Telo - TAGGG hTERT定量试剂盒和LightCycler技术，对26例正常及64例细胞学异常标本的hTERT启动子基因甲基化状态和hTERT mRNA进行定量研究。同时也评估了E6/E7 HPV - 16 mRNA表达情况。在正常及癌前宫颈标本中，未观察到hTERT mRNA表达与hTERT启动子甲基化之间以及端粒酶活性与hTERT启动子甲基化之间存在显著相关性。在72%的HPV - 16感染样本中观察到E6/E7 HPV - 16 mRNA表达，且其与hTERT mRNA表达和端粒酶活性相关（P < 0.05）。这是第一项研究hTERT启动子甲基化在癌前病变中hTERT mRNA表达和端粒酶活性作用的研究。观察到的缺乏相关性表明可能有其他机制参与hTERT表达的调控。hTERT mRNA与E6/E7 mRNA表达之间的相关性证实了HPV感染在hTERT调控中的作用。
