Journal
NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS
Volume 25, Issue 9-11, Pages 1001-1007Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15257770600890269
Keywords
gemcitabine; drug resistance; ribonucleotide reductase; micro-array
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To study in detail the relation between gene expression and resistance against gemcitabine, a cell line was isolated from a tumor for which gemcitabine resistance was induced in vivo. Similar to the in vivo tumor, resistance in this cell line, C 26-G, was not related to deficiency of deoxycytidine kinase (dCK). Micro-array analysis showed increased expression of ribonucleotide reductase (RR) subunits M1 and M2 as confirmed by real time PCR analysis (28- and 2.7-fold, respectively). In cell culture, moderate cross-resistance (about 2-fold) was observed to 1-beta-Darabinofuranosylcytosine (ara-C), 2-chloro-2'deoxyadenosine (CdA), LY231514 (ALIMTA), and cisplatin (CDDP), and pronounced cross-resistance (> 23-fold) to 2', 2'-difluorodeoxyuridine (dFdU) and 2', 2'-difluorodeoxyguanosine (dFdG). Culture in the absence of gemcitabine reduced resistance as well as RRM1 RNA expression, demonstrating a direct relationship of RRM1 RNA expression with acquired resistance to gemcitabine.
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