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Published on: October 15, 2018
Aberrant gene expression in human non small cell lung carcinoma cells exposed to demethylating agent
Bao-Zhu Yuan1, Amy M Jefferson, Nicholas C Popescu
1Laboratory 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
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.
Insights
This study investigated gene expression changes in lung cancer cells treated with 5-aza-2'-deoxycytidine (5-aza-dC). Upregulation of Hint/PKCI-1 showed potential as a tumor suppressor, inhibiting cancer cell growth and tumorigenicity.
Area of Science:
- Molecular Biology
- Cancer Research
- Epigenetics
Background:
- Understanding cancer development requires identifying genes with genetic or epigenetic alterations.
- Epigenetic modifications, like those induced by 5-aza-2'-deoxycytidine (5-aza-dC), play a crucial role in carcinogenesis.
Purpose of the Study:
- To identify genes altered by 5-aza-dC treatment in human lung cancer cells.
- To investigate the role of upregulated genes, particularly Hint/PKCI-1, in lung cancer progression.
Main Methods:
- Gene expression profiling using cDNA array analysis on non-small cell lung cancer (NSCLC) cell lines.
- Treatment of NSCLC cell line NCI-H522 with 5-aza-dC.
- In vitro and in vivo studies of Hint/PKCI-1 gene transfer.
Main Results:
- 5-aza-dC treatment upregulated 16 genes and downregulated 14 genes in NSCLC cells.
- Hint/PKCI-1 gene was significantly upregulated by 5-aza-dC.
- Hint/PKCI-1 gene transfer inhibited in vitro growth and reduced in vivo tumorigenicity of NSCLC cells.
Conclusions:
- Hint/PKCI-1, a histidine triad (HIT) nucleotide-binding protein, may be involved in lung carcinogenesis.
- The study suggests Hint/PKCI-1's potential as a therapeutic target for lung cancer.
