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Aberrant gene expression in human non small cell lung carcinoma cells exposed to demethylating agent 5-aza-2 '-deoxycytidine.

Authors
Yuan-B; Jefferson-A; Popescu-NC; Reynolds-SH
Source
Neoplasia 2004 Jul-Aug; 6(4):412-419
NIOSHTIC No.
20031563
Abstract
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.
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
Contact
BZ Yuan, Laboratory of Cancer Genetics, Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505
CODEN
NEOPFL
Publication Date
20040701
Document Type
Journal Article
Email Address
bby1@cdc.gov
Fiscal Year
2004
NTIS Accession No.
NTIS Price
ISSN
1476-5586
NIOSH Division
HELD
Source Name
Neoplasia
State
WV
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