Micro-Array Analysis of Resistance for Gemcitabine Results in Increased Expression of Ribonucleotide Reductase Subunits
Copyright policy )Micro-Array Analysis of Resistance for Gemcitabine Results in Increased Expression of Ribonucleotide Reductase Subunits
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.
- Amsterdam UMC Netherlands
- Amsterdam University Medical Centers Netherlands
- Amsterdam UMC, location VUmc Netherlands
Micro-array, Guanine, Reverse Transcriptase Polymerase Chain Reaction, Cytarabine, Antineoplastic Agents, Pemetrexed, Deoxycytidine, Gemcitabine, Gene Expression Regulation, Neoplastic, Inhibitory Concentration 50, Glutamates, Drug Resistance, Neoplasm, Drug resistance, Cell Line, Tumor, Ribonucleotide Reductases, Cladribine, Humans, Cisplatin, Drug Screening Assays, Antitumor, Ribonucleotide reductase, Oligonucleotide Array Sequence Analysis
Micro-array, Guanine, Reverse Transcriptase Polymerase Chain Reaction, Cytarabine, Antineoplastic Agents, Pemetrexed, Deoxycytidine, Gemcitabine, Gene Expression Regulation, Neoplastic, Inhibitory Concentration 50, Glutamates, Drug Resistance, Neoplasm, Drug resistance, Cell Line, Tumor, Ribonucleotide Reductases, Cladribine, Humans, Cisplatin, Drug Screening Assays, Antitumor, Ribonucleotide reductase, Oligonucleotide Array Sequence Analysis
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