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KMID : 1001020060040020062
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Journal of Urologic Oncology
2006 Volume.4 No. 2 p.62 ~ p.67
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DNA Microarray Analysis of the Genetic Expression in a Cisplatin-resistant Bladder Tumor Cell Line
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Lee Sang-Cheol
Byun Seok-Soo
Lee Eun-Sik
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Abstract
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Purpose: Cisplatin is a standard chemotherapeutic agent used in the treatment of advanced bladder cancer. However, the value of cisplatin in chemotherapy is limited by the resistance of tumor cells to this drug. This study was designed to investigate the mechanism of cisplatin-resistance by performing a comparative microarray analysis of gene expression between human bladder cancer cells(T24) and cisplatin-resistant human bladder cancer cells(T24R2).
Materials and Methods :The bladder cancer cell line, resistant at 2.0μg/ml of cisplatin(T24R2) was established by stepwise incremental exposure of the parent cell line(T24) to cisplatin, starting with 10ng/ml. We performed global gene expression analyses of the T24 and T24R2 cell lines, using DNA microarrays. The gene expression pattern of T24R2 was compared with that of T24 using the fold-change and the binomial test in PANTHER(Protein ANalysis THrough Evolutionary Relationships) ontology system. The up-regulated genes in T24R2 compared to T24 were confirmed by reverse transcription-polymerase chain reaction(RT-PCR).
Results: The up-regulated and down-regulated genes of T24R2 were compared to that of T24. The four-fold change was used as criteria for clustering in the PANTHER system. Two biological processes were significantly activated in T24R2, which were the inhibition of apoptosis and oncogene. The up-regulated genes in the apoptosis inhibition in T24R2 included NF-kB, Bcl-2A1, BIRC3, STAT1, IL-6 and IL-15. Elevated expression of these genes was confirmed by RT-PCR.
Conclusions : The inhibition of apoptosis may play an important role in cisplatin resistance of T24R2 bladder cancer cell line.
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KEYWORD
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Bladder neoplasm, Cisplatin, Microarray analysis
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