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Korean Journal of Obstetrics & Gynecology 2002;45(12):2280-2288.
Published online December 1, 2002.
Analysis of HPV-16 E6-related gene expression using cDNA microarray.
Jin Myeong, Sun Young Rha, Myoung Jin Lee, Soo Jong Um, Sung Eun Namkoong, Jong Sup Park
1Department of Obstetrics and Gynecology, Catholic University Medical College, Korea.
2Cancer Metastasis Research Center, Yonsei University, Korea.
3Department of Life Science, Sejong University, Korea.
Abstract
OBJECTIVE
To examine the effect of HPV-16 E6 expression on the transcription of cellular genes, we used cDNA microarray in HPV-16 E6 transfected stable cancer cell lines. METHODS: Using cDNA microarray consisting of 1,024 genes, we have performed a systematic characterization of gene expression in A549E6 human lung adenocarcinoma and RC10.1 human colon adenocarcinoma cell lines stably expressing HPV-16 E6 gene. The up-regulated and down-regulated genes were classified into the different functional categories; oncogenes, apoptosis, cell cycle, signal transduction, gene regulation, immune response, cell adhesion, protein transport, metabolism, redox control and angiogenesis. RESULTS: Among 1,024 known genes and ESTs (expressed sequence tags) tested, we found 27 up- regulated and 43 down-regulated genes in A549E6 (HPV-16 E6) compared to A549. The major up-regulated genes were as follows. GTPase-activating protein Rho 4, transcription factor D2, IKAROS, integrin-alpha 6, cadherin 11, ephrin-beta 2, RAN binding protein 2, branched-chain amino transferase 2. The major down-regulated genes were as follows. K-ras 2, CDC (cell division cycle) 37, CDC16, CDC7L1, IRF3, interferon-gamma-inducible protein 30, cadherin 6, desmoglein 1, desmocollin 2, endothelin 2. Also, we found 48 up-regulated and 34 down-regulated genes in RC10.1 (HPV-16 E6) compared to RKO. The major up-regulated genes were as follows. Colon cancer familial nonpolyposis type 1 (COCA 1), Bcl 2, jagged 1, MAP2K6, E2F1, ephrin receptor-beta 2, ephrin-beta 2, desmoglein 1, transforming growth factor-beta 3. The major down-regulated genes were as follows. KIT, Rad51C, Bcl 2 antagonist killer 1, STAT 4, epidermal growth factor receptor, high mobility group protein 2, cadherin 11, cadherin 12, cadherin 3, integrin-alpha 1, intergrin-alpha 8, chromosome segregation 1-like. CONCLUSION: Various expression patterns of cellular genes by HPV-16 E6 could be wholy grasped and classified into different functional groups using both cell line system stably expressed HPV-16 E6 and cDNA microarray analysis. These analysis methods must be helpful to understand multiple effects of a specific gene on cellular genes in a short period.
Key Words: Human papillomavirus, cDNA microarray, Cellular genes, HPV-16 E6


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