Micro-Array Analysis of Resistance for Gemcitabine Results in Increased Expression of Ribonucleotide Reductase Subunits |
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| Authors: | K Smid A M Bergman P P Eijk G Veerman V W T Ruiz van Haperen P van den Ijssel |
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| Institution: | 1. Department of Medical Oncology , VU University Medical Center , Amsterdam, the Netherlands;2. Micro-array Facility , VU University Medical Center , Amsterdam, the Netherlands;3. Department of Medical Oncology , VU University Medical Center and New Drug Development Office , Amsterdam, the Netherlands;4. Department of Medical Oncology , VU University Medical Center and Raad voor Gezondheidsonderzoek (RGO) , The Hague, the Netherlands |
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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. |
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| Keywords: | Gemcitabine Drug resistance Ribonucleotide reductase Micro-array |
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