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 underexpressed genes were 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 lines. 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 underexpressed. The acquisition of resistance to 5FU by tumor cells may result from multiple changes in cellular functions.
Takechi
T
T
The Second Cancer Research Laboratory, Taiho Pharmaceutical Co., Ltd., 1-27 Misugidai, Hanno, Saitama 357-8527, Japan. ttakechi@taiho.co.jp
Koizumi
K
K
Tsujimoto
H
H
Fukushima
M
M
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D015152:Blotting, Northern; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology*; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000964:Antimetabolites, Antineoplastic; D018076:DNA, Complementary; D012333:RNA, Messenger; D005472:Fluorouracil