Aberrant Gene Expression in Human Non Small Cell Lung Carcinoma Cells Exposed to Demethylating Agent 5-Aza-2 ‘-Deoxycytidine

Details

• Personal Author:
  Jefferson A ; Popescu NC ; Reynolds SH ; Yuan B
• Description:
  The identification of genes undergoing genetic or epigenetic alterations and contributing to the development of cancer is critical to our understanding of the molecular mechanisms of carcinogenesis. A new approach in identifying alterations of genes that might be relevant to the process of tumor development was used in this study by examining the gene expression profile in human lung cancer cells exposed to 5-aza-2'-deoxycytidine (5-aza-dC). A cDNA array analysis was carried out on 5-aza-dC-treated and untreated non small cell lung cancer (NSCLC) cell line NCI-H522. Sixteen and 14 genes were upregulated and downregulated, respectively, by 5-aza-dC treatment. Among them, downregulation of tyrosine protein kinase ABL2 (ABL2) gene and upregulation of hint/protein kinase C inhibitor 1 (Hint/PKCI-1), DVL1, TIMP-1, and TRP-1 genes were found in expanded observations in two or three of five 5-aza-dC-treated NSCLC cell lines. Among these genes, we found that cDNA transfer of Hint/PKCI-1 resulted in a significant in vitro growth inhibition in two cell lines exhibiting 5-aza-dC-induced upregulation of Hint/PKCI-1 and significantly reduced in vivo tumorigenicity of one NSCLC cell line. Hint/PKCI-1, which is the only other characterized human histidine triad (HIT) nucleotide-binding protein in addition to tumor-suppressor gene FHIT, might be involved in lung carcinogenesis. [Description provided by NIOSH]
• Subjects:
  Lung Lung Diseases Neoplasms Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Cancer Cell-biology Cell-function Cell-growth Cell-metabolism Cell-transformation Cellular-uptake Lung-cancer Lung-cells Lung-disease Pulmonary-cancer Pulmonary-disorders Pulmonary-system-disorders

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• ISSN:
  1476-5586
• 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:
  412-419
• Volume:
  6
• Issue:
  4
• NIOSHTIC Number:
  nn:20031563
• Citation:
  Neoplasia 2004 Jul-Aug; 6(4):412-419
• Contact Point Address:
  BZ Yuan, Laboratory of Cancer Genetics, Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505
• Email:
  bby1@cdc.gov
• Federal Fiscal Year:
  2004
• Peer Reviewed:
  True
• Source Full Name:
  Neoplasia
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c7368cde7903eb96d4be2c86082f326f7f0e4be59eadba996e9a664471cec6166d7661d7cb1df57d4c3cd0fca80ae14d5b8c7fecd97341749d2337d5b0504ea7
• Download URL:
  https://stacks.cdc.gov/view/cdc/185813/cdc_185813_DS1.pdf
• File Type:
  [PDF - 230.57 KB ]