Cancer Lett. 2011 Jan 1;300(1):79-86.

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

Daskalos A, Logotheti S, Markopoulou S, Xinarianos G, Gosney JR, Kastania AN, Zoumpourlis V, Field JK, Liloglou T.
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.
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Sp1 binds to the external promoter of the p73 gene and induces the expression of TAp73gamma in lung cancer.
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