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KMID : 0379520040200020109
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한국독성학회지
2004 Volume.20 No. 2 p.109 ~ p.116
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Differential Gene Expression after Adenovirus-Mediated p16 Gene Transfer in Human Non-Small Cell Lung Cancer Cells
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Park Mi-Sun
Kim Ok-Hee
Park Hyun-Shin
Jee Seung-Wan
Eom Mi-Ok
Ryeom Tai-Kyung
Kang Ho-Il
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Abstract
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For the safety evaluation of adenovirus-mediated gene transfer, we investigated differential gene expressions after transfecting adenoviral vector containing p16 tumor suppressor gene (Ad5CMV-p16) into human non-small cell lung cancer cells. In the previous study, we showed adenovirus-mediated p16^{INK4a} gene transfer resulted in significant inhibition of cancer cell growth. We investigated gene expression changes after transfecting Ad5CMV-p16, Ad5CMV (null type, a mock vector) into A549 cells by using cDNA chip and oligonucleotide microarray chip (1200 genes) which carries genes related with signal transduction pathways, cell cycle regulations, oncogenes and tumor suppressor genes. We found that p16^{INK4a} gene transfer down regulated 5 genes (cdc2, cyclin D3, cyclin B, cyclin E, cdk2) among 26 genes involved in cell cycle regulations. Compared with serum-free medium treated cells, Ad5CMV-p16 changed 27 gene expressions, two fold or more on oligonucleotide chip. In addition, Ad5CMV-p16 did not seem to increase the tumorigenicity-related gene expression in A549 cells. Further studies will be needed to investigate the effect of Ad5CMV-p16 on normal human cells and tissues for safety evaluation.
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KEYWORD
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Gene therapy, Safety evaluation, Adenoviral vector, p16, DNA microarray.
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