Screening of differentially expressed genes in 5-fluorouracil-resistant human gastrointestinal tumor cells

To identify genes differentially expressed in association with resistance to 5-fluorouracil (5FU), an mRNA differential display (DD) analysis was used to compare transcripts from the NUGC-3 human gastric tumor cell line and the NUGC-3/5FU/L line, which had acquired 208-fold resistance as a consequence of repeated exposure to escalating concentrations of 5FU, The 110 cDNA fragments differentially expressed in the DD analysis of either the NUGC-3 or NUGC-3/5FU/L cells were sequenced and subjected to a homology search, and 29 overexpressed and 22 underespressed genes Mere identified in NUGC-3/5FU/L as a result, To confirm whether the changes in the gene expression levels in the NUGC-3/5FU/L cells were shared by other 5FU-resistant cells, 35 genes were analyzed by northern hybridization in 3 pairs of parent/5FU-resistant human gastrointestinal tumor cell lints, The analysis revealed 20 overexpressed and 10 underexpressed genes in at least one of the three 5FU-resistant cells as compared with those in the parent cells, Among them, P-glycoprotein, equilibrative nucleoside transporter 1, and methylenetetrahydrofolate dehydrogenase were highly expressed in two of the three 5FU-resistant cells and cytidine deaminase and integrin alpha3 were underespressed, The acquisition of resistance to 5FU by. tumor cells may result from multiple changes in cellular functions.