Chemo-resistance-related genes detected by cDNA microarray

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To identify chemoresistance-related genes of gastric cancer, we utilized cDNA microarray technology. Thirty-five gastric cancer specimens surgically resected at our institute between 1998 and 1999 were studied for quantification of 6,300 gene expression by means of oligonucleotide microarray methods, and the calculated gene expressions were evaluated comparing with chemoresistance of each specimens, which was determined by MTT assay (the tetrazolium-based 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide assay). Inhibition rates (IR) were determined for cisplatin (DDP), 5-fluorouracil (5-FU), mitomycin C or doxorubicin. IR more than or equal to 60% was regarded as sensitive to each agent, and IR less than 40% defined as resistant. Clustering was successfully completed for DDP, resulting in selection of 23 candidates as DDP resistance-related genes, including vascular permeability factor, 2 membrane transporting subunits, and retinoblastoma-binding protein-1. In addition, fur … More ther selection of the DDP resistance-related genes was performed following to these two criteria ; 1)Expression of its gene can be detected in more than 70% of the resistant tumors. 2)Expression detected in less than 30% of the sensitive tumors. 3)Expression levels in tumors twice that of normal mucosa in more than 50% of specimens. Then, metallothionein-IG and heparin-binding epidermal growth factor-like growth factor (HB-EGF) were identified as candidates of DDP-resistance-related genes. When known resistance-related genes to DDP were analyzed according to the MTT assay result, a family of glutathione-S-transferase and cyclooxygenase-2 genes were also evaluated as resistance-related genes. For 5-FU resistance, expression of dihydropyiimidine dehydrogenase and heparin-binding EGF-like growth factor genes were also suggested to be 5-FU resistance-related genes. The present study demonstrated that oligonucleotide microarrays would be useful in providing further information regarding chemoresistant-factors in cancer. Less