Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

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

Authors
Zhang-P; Wang-J; Gao-W; Yuan-B; Rogers-J; Reed-E
Source
Mol Cancer 2004 May; 3(1):14
NIOSHTIC No.
20025486
Abstract
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. 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. 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.
Keywords
Lung-cancer; Cancer; Pulmonary-system-disorders; Respiratory-system-disorders; Mammalian-cells; Tumors; Laboratory-animals; Animals; Animal-studies; Mutagenesis; Mutagenicity
Contact
Department of Pathology, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV 26506-9203
Publication Date
20040504
Document Type
Journal Article
Email Address
pzhang@hsc.wvu.edu
Fiscal Year
2004
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
1476-4598
NIOSH Division
HELD
Source Name
Molecular Cancer
State
WV
TOP