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

doi:10.1016/j.canlet.2010.09.009

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

Medical School

Liverpool University Hospitals NHS Foundation Trust
Roy Castle Lung Cancer Foundation

Research output: Contribution to journal › Article (journal) › peer-review

51 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 language	English
Pages (from-to)	79-86
Number of pages	8
Journal	Cancer Letters
Volume	300
Issue number	1
DOIs	https://doi.org/10.1016/j.canlet.2010.09.009
Publication status	Published - 1 Jan 2011

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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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10.1016/j.canlet.2010.09.009

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@article{cfaea8a672cf4522ae10d62849ab159e,

title = "Global DNA hypomethylation-induced ΔNp73 transcriptional activation in non-small cell lung cancer",

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.",

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",

author = "Alexandros Daskalos and Stella Logotheti and Soultana Markopoulou and George Xinarianos and Gosney, \{John R\} and Kastania, \{Anastasia N\} and Vassilis Zoumpourlis and Field, \{John K\} and Triantafillos Liloglou",

year = "2011",

month = jan,

day = "1",

doi = "10.1016/j.canlet.2010.09.009",

language = "English",

volume = "300",

pages = "79--86",

journal = "Cancer Letters",

issn = "0304-3835",

publisher = "Elsevier Ireland Ltd",

number = "1",

}

TY - JOUR

T1 - Global DNA hypomethylation-induced ΔNp73 transcriptional activation in non-small cell lung cancer

AU - Daskalos, Alexandros

AU - Logotheti, Stella

AU - Markopoulou, Soultana

AU - Xinarianos, George

AU - Gosney, John R

AU - Kastania, Anastasia N

AU - Zoumpourlis, Vassilis

AU - Field, John K

AU - Liloglou, Triantafillos

PY - 2011/1/1

Y1 - 2011/1/1

N2 - 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.

AB - 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.

KW - Adenocarcinoma/genetics

KW - Aged

KW - Aged, 80 and over

KW - Carcinoma, Non-Small-Cell Lung/genetics

KW - Carcinoma, Squamous Cell/genetics

KW - DNA Methylation

KW - DNA-Binding Proteins/genetics

KW - Female

KW - Humans

KW - Lung Neoplasms/genetics

KW - Male

KW - Middle Aged

KW - Nuclear Proteins/genetics

KW - Promoter Regions, Genetic

KW - Transcriptional Activation

KW - Tumor Protein p73

KW - Tumor Suppressor Proteins/genetics

U2 - 10.1016/j.canlet.2010.09.009

DO - 10.1016/j.canlet.2010.09.009

M3 - Article (journal)

C2 - 20926182

SN - 0304-3835

VL - 300

SP - 79

EP - 86

JO - Cancer Letters

JF - Cancer Letters

IS - 1

ER -

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

Abstract

UN SDGs

Keywords

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