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

Alexandros Daskalos, Stella Logotheti, Soultana Markopoulou, George Xinarianos, John R Gosney, Anastasia N Kastania, Vassilis Zoumpourlis, John K Field, Triantafillos Liloglou

Research output: Contribution to journalArticle (journal)peer-review

49 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)79-86
Number of pages8
JournalCancer Letters
Volume300
Issue number1
DOIs
Publication statusPublished - 1 Jan 2011

Keywords

  • Adenocarcinoma/genetics
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung/genetics
  • Carcinoma, Squamous Cell/genetics
  • DNA Methylation
  • DNA-Binding Proteins/genetics
  • Female
  • Humans
  • Lung Neoplasms/genetics
  • Male
  • Middle Aged
  • Nuclear Proteins/genetics
  • Promoter Regions, Genetic
  • Transcriptional Activation
  • Tumor Protein p73
  • Tumor Suppressor Proteins/genetics

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