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 language | English |
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Pages (from-to) | 79-86 |
Number of pages | 8 |
Journal | Cancer Letters |
Volume | 300 |
Issue number | 1 |
DOIs | |
Publication status | Published - 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