Global DNA hypomethylation-induced ΔNp73 transcriptional activation in non-small cell lung cancer

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• 作者：Alex ; ros Daskalos ; Stella Logotheti ; Soultana Markopoulou ; George Xinarianos ; John R. Gosney ; Anastasia N. Kastania ; Vassilis Zoumpourlis ; John K. Field ; Triantafillos Liloglou
• 关键词：Lung cancer ; p73 ; DNA methylation ; &#x394 ; &#x39d ; p73 ; TAp73
• 刊名：Cancer Letters
• 出版年：2011
• 出版时间：1 January 2011
• 年：2011
• 卷：300
• 期：1
• 页码：79-86
• 全文大小：630 K

文摘

p73 possesses an extrinsic P1 promoter and an intrinsic P2 promoter controlling the expression of the pro-apoptotic TAp73 isoforms and the anti-apoptotic ΔΝp73 isoforms respectively. In this study, we investigated the DNA methylation status of both promoters as a means of epigenetic transcriptional control of their corresponding isoforms in 102 primary non-small cell lung carcinomas (NSCLCs). We demonstrated that while P1 hypermethylation-associated reduction of TAp73 mRNA levels is relatively infrequent, the P2 hypomethylation-associated over-expression of ΔΝp73 mRNA is a frequent event, particularly among squamous cell carcinomas. P2 hypomethylation strongly correlated with LINE-1 element hypomethylation, indicating that ΔΝp73 over-expression may be a passive consequence of global DNA hypomethylation.