Identification of novel genes associated with the response to 5-FU treatment in gastric cancer cell lines using a cDNA microarray.
The 5-Fluorouracil (5-FU) is an anticancer drug that is widely used in the treatment of cancer. To identify novel genes associated with 5-FU in gastric cancer, the time-dependent expression profiling of genes in response to 5-FU was examined in 5-FU sensitive and/or resistant gastric cancer cell lines using a 'KUGI 14 K cDNA chip' containing 14,081 unigenes obtained from human gastric cancer cell lines and tissues. By this analysis, we obtained 13 genes which are directly associated with sensitivity or resistance to 5-FU. Of these genes, 11 were found to be commonly up-regulated only in the 5-FU sensitive cell lines, and 2 were oppositely regulated in both of 5-FU sensitive and resistant cell lines. These genes were determined to be involved in cell surface, apoptosis, cell cycle and signal transduction. Of these genes, the expression levels of ZFP100, 4F2hc, FLJ11021, CSTF3, PPP1R14A, DDB2, C6orf139, CDKN1A, HOXC11 and FLJ38860 were confirmed by semi-quantitative RT-PCR. In addition, seven genes containing RRMI, UP1 and K-EST0037597 were found to be commonly up-regulated in both cell lines. In addition, the expression of genes such as TP, OPRT, TS and DPD, which have been previously known to be involved in 5-FU metabolism, were examined in both of 5-FU sensitive and resistant cell lines. These results provide not only predictive biomarkers for 5-FU sensitivity or resistance to human gastric cancer, but also a new molecular basis for understanding the mechanism of cellular cytoxicity to 5-FU.
Laboratory of Human Genomics, Division of Genomics and Proteomics, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-333, South Korea.
Ji-Seon
JS
Park
Sun
S
Young Yoon
Jeong-Min
JM
Kim
Young-Il
YI
Yeom
Yong Sung
YS
Kim
Nam-Soon
NS
Kim
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D014408:Biomarkers, Tumor; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology*; D020869:Gene Expression Profiling; D006801:Humans; D007700:Kinetics; D020411:Oligonucleotide Array Sequence Analysis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D005472:Fluorouracil