PMID- 15256063 OWN - NLM STAT- MEDLINE DCOM- 20050412 LR - 20181130 IS - 1522-8002 (Print) IS - 1476-5586 (Electronic) IS - 1476-5586 (Linking) VI - 6 IP - 4 DP - 2004 Jul-Aug TI - Aberrant gene expression in human non small cell lung carcinoma cells exposed to demethylating agent 5-aza-2'-deoxycytidine. PG - 412-9 AB - 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. CI - Copyright 2004 Neoplasia Press, Inc. FAU - Yuan, Bao-Zhu AU - Yuan BZ AD - Laboratory of Cancer Genetics, Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505, USA. bby1@cdc.gov FAU - Jefferson, Amy M AU - Jefferson AM FAU - Popescu, Nicholas C AU - Popescu NC FAU - Reynolds, Steven H AU - Reynolds SH LA - eng PT - Journal Article PL - United States TA - Neoplasia JT - Neoplasia (New York, N.Y.) JID - 100886622 RN - 0 (Antimetabolites, Antineoplastic) RN - 776B62CQ27 (Decitabine) RN - M801H13NRU (Azacitidine) SB - IM MH - Antimetabolites, Antineoplastic/toxicity MH - Apoptosis/drug effects MH - Azacitidine/*analogs & derivatives/*toxicity MH - Carcinoma, Non-Small-Cell Lung MH - Cell Division/drug effects MH - Cell Line, Tumor MH - DNA Methylation MH - Decitabine MH - Gene Expression Regulation, Neoplastic/*drug effects MH - Humans MH - Kinetics MH - Lung Neoplasms MH - Oligonucleotide Array Sequence Analysis MH - Transfection PMC - PMC1502114 EDAT- 2004/07/17 05:00 MHDA- 2005/04/13 09:00 PMCR- 2004/07/01 CRDT- 2004/07/17 05:00 PHST- 2004/07/17 05:00 [pubmed] PHST- 2005/04/13 09:00 [medline] PHST- 2004/07/17 05:00 [entrez] PHST- 2004/07/01 00:00 [pmc-release] AID - 03490 [pii] AID - 10.1593/neo.03490 [doi] PST - ppublish SO - Neoplasia. 2004 Jul-Aug;6(4):412-9. doi: 10.1593/neo.03490.