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

K. Smid, A. M. Bergman, P. P. Eijk, G. Veerman, V. W.T. Ruiz Van Haperen, P. Van Den Ijssel, B. Ylstra, G. J. Peters

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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-β-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.

Original languageEnglish
Pages (from-to)1001-1007
Number of pages7
JournalNucleosides, Nucleotides and Nucleic Acids
Volume25
Issue number9-11
DOIs
Publication statusPublished - 1 Jun 2006

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