CHK2 Kinase Expression Is Down-Regulated Due to Promoter Methylation in Non-Small Cell Lung Cancer

Details

• Personal Author:
  Gao W ; Reed E ; Rogers J ; Wang J ; Yuan B ; Zhang P
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Animals Laboratories Lung Lung Diseases Mutagens Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Animal-studies Cancer Laboratory-animals Lung-cancer Mammalian-cells Mutagenesis Mutagenicity Pulmonary-system-disorders Respiratory-system-disorders Tumors
• ISSN:
  1476-4598
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  14
• Volume:
  3
• Issue:
  1
• NIOSHTIC Number:
  nn:20025486
• Citation:
  Mol Cancer 2004 May; 3(1):14
• Contact Point Address:
  Department of Pathology, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV 26506-9203
• Email:
  pzhang@hsc.wvu.edu
• Federal Fiscal Year:
  2004
• Peer Reviewed:
  True
• Source Full Name:
  Molecular Cancer
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:cd71df229dc7fbd4aa1a43c75a70277cec7f920e24c456c9c2a512ced5605a584b1ac538bb66a4b7abc23ffe60e48f160e3c835e839f7068ca4cad2073430a21
• Download URL:
  https://stacks.cdc.gov/view/cdc/196831/cdc_196831_DS1.pdf
• File Type:
  [PDF - 1.78 MB ]