Document Type
Article
Publication Date
2004
College/Unit
School of Medicine
Department/Program/Center
Medicine
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.
Digital Commons Citation
Zhang, Peilin; Wang, Jie; Gao, Weiyi; Yuan, Bao-Zhu; Rogers, John; and Reed, Eddie, "CHK2 kinase expression is down-regulated due to promoter methylation in non-small cell lung cancer" (2004). Faculty & Staff Scholarship. 2885.
https://researchrepository.wvu.edu/faculty_publications/2885
Source Citation
Zhang, P., Wang, J., Gao, W. et al. CHK2 kinase expression is down-regulated due to promoter methylation in non-small cell lung cancer. Mol Cancer 3, 14 (2004). https://doi.org/10.1186/1476-4598-3-14
Comments
© 2004 Zhang et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.