Cancer Res Treat.  2005 Feb;37(1):54-62.

cDNA Microarray Analysis of Differential Gene Expression in Gastric Cancer Cells Sensitive and Resistant to 5-Fluorouracil and Cisplatin

• Ahn MJ
• Yoo YD
• Lee KH
• Ahn JI
• Yu DH
• Lee HS
• Oh HS
• Choi JH
• Lee YS

Abstract

PURPOSE
Gastric cancer is one of the most prevalent cancers worldwide. 5-fluorouracil (5-FU) and cisplatin are the most commonly used drugs for the treatment of gastric cancer. However, a significant number of tumors often fail to respond to chemotherapy. MATERIALS AND METHODS: To better understand the molecular mechanisms underlying drug resistance in gastric cancer the gene expression in gastric cancer cells, which were either sensitive or resistant to 5-FU and cisplatin, were examined using cDNA microarray analysis. To confirm the differential gene expression, as determined using the microarray, semiquantitative RT-PCR was performed on a subset of differentially expressed cDNAs. RESULTS: 69 and 45 genes, which were either up-regulated (9 and 22 genes) or down-regulated (60 and 25 genes), were identified in 5-FU- and cisplatin-resistant cells, respectively. Several genes, such as adaptor-related protein complex 1 and baculoviral IAP repeat-containing 3, were up-regulated in both drug-resistant cell types. Several genes, such as the ras homolog gene family, tropomyosin, tumor rejection antigen, protein disulfide isomerase-related protein, melanocortin 1 receptor, defensin, cyclophilin B, dual specificity phosphatase 8 and hepatocyte nuclear factor 3, were down-regulated in both drug-resistant cell types. CONCLUSION: These findings show that cDNA microarray analysis can be used to obtain gene expression profiles that reflect the effect of anticancer drugs on gastric cancer cells. Such data may lead to the assigning of signature expression profiles of drug-resistant tumors, which may help predict responses to drugs and assist in the design of tailored therapeutic regimens to overcome drug resistance.

Keyword

cDNA microarray; Stomach neoplasms; 5-fluorouracil; Cisplatin; Drug resistance

MeSH Terms

Adaptor Protein Complex 1
Cisplatin*
Cyclophilins
DNA, Complementary*
Drug Resistance
Drug Therapy
Dual-Specificity Phosphatases
Fluorouracil*
Gene Expression*
Hepatocytes
Humans
Oligonucleotide Array Sequence Analysis*
Receptor, Melanocortin, Type 1
Stomach Neoplasms*
Transcriptome
Tropomyosin
Adaptor Protein Complex 1
Cisplatin
Cyclophilins
DNA, Complementary
Dual-Specificity Phosphatases
Fluorouracil
Receptor, Melanocortin, Type 1
Tropomyosin

Figure

• 

  Fig. 1 Semi-quantitative RT-PCR analysis of the gene expressions in 5-FU-resistant cells. The left panel shows the RT-PCR results. The right panel indicates the relative mRNA ratios of the indicated genes. (A) The expressions of seven genes are shown to be up-regulated by the microarray analysis; follistatin, keratin 7, protein complex 1 mu 2 subunit, baculoviral IAP repeat-containing 2, pregnancy-induced growth inhibitor, MnSOD and cytochrome p450. (B) The expression of one gene is shown to be down-regulated by the microarray analysis; transmembrane protein 3.

• 

  Fig. 2 Semi-quantitative RT-PCR analysis of the gene expressions in cisplatin-resistant cells. The left panel shows the RT-PCR results. The right panel indicates the relative mRNA ratios of the indicated genes. (A) The expressions of four genes are shown to be up-regulated by the microarray analysis; transmembrane protein 3, protein complex 1 mu 2 subunit, baculoviral IAP repeat-containing 2 and pregnancy-induced growth inhibitor. (B) The expressions of four genes are shown to be down-regulated by the microarray analysis; follistatin, keratin 7, MnSOD and cytochrome p450.

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