Micro-array analysis of resistance for gemcitabine results in increased expression of ribonucleotide reductase subunits.

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Smid K, Bergman AM, Eijk PP, Veerman G, van Haperen VW, van den Ijssel P, Ylstra B, Peters GJ

Micro-array analysis of resistance for gemcitabine results in increased expression of ribonucleotide reductase subunits.

Nucleosides Nucleotides Nucleic Acids. 2006;25(9-11):1001-7.

PubMed ID

17065054 [ View in PubMed

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Abstract

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-ss-D-arabinofuranosylcytosine (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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Gemcitabine	Ribonucleoside-diphosphate reductase large subunit	Protein	Humans	Yes	Inhibitor	Details