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Molecular Cancer
Published in: Molecular Cancer 1/2004

Open Access 01-12-2004 | Research

CHK2 kinase expression is down-regulated due to promoter methylation in non-small cell lung cancer

Authors: Peilin Zhang, Jie Wang, Weiyi Gao, Bao-Zhu Yuan, John Rogers, Eddie Reed

Published in: Molecular Cancer | Issue 1/2004

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Abstract

Background

CHK2 kinase is a tumor suppressor that plays important role in DNA damage signaling, cell cycle regulation and DNA damage induced apoptosis. CHK2 kinase expression was known to be ubiquitous in mammalian cells. CHK2-/- cells were remarkably resistant to DNA damage induced apoptosis, mimicking the clinical behavior of non-small cell lung cancer to conventional chemo and radiation therapy.

Result

We reported that the CHK2 expression is diminished or absent in both non-small cell lung cancer (NSCLC) cell lines and clinical lung cancer tumor specimens. The absent CHK2 expression in NSCLC was due to hypermethylation of the CHK2 gene promoter, preventing from binding of a transcriptional factor, leading to silence of the CHK2 gene transcription.

Conclusion

Since the CHK2 null mice showed a remarkable radioresistance, which bear significant similarity to clinical behavior of NSCLC, down-regulation of CHK2 kinase expression by CHK2 gene silencing and methylation in non-small cell lung cancer suggest a critical role of CHK2 kinase in DNA damage induced apoptosis and a novel mechanism of the resistance of NSCLC to DNA damage based therapy.
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Metadata
Title
CHK2 kinase expression is down-regulated due to promoter methylation in non-small cell lung cancer
Authors
Peilin Zhang
Jie Wang
Weiyi Gao
Bao-Zhu Yuan
John Rogers
Eddie Reed
Publication date
01-12-2004
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2004
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-3-14

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