TY - JOUR
T1 - Micro-array analysis of resistance for gemcitabine results in increased expression of ribonucleotide reductase subunits
AU - Smid, K.
AU - Bergman, A. M.
AU - Eijk, P. P.
AU - Veerman, G.
AU - Ruiz Van Haperen, V. W.T.
AU - Van Den Ijssel, P.
AU - Ylstra, B.
AU - Peters, G. J.
PY - 2006/6/1
Y1 - 2006/6/1
N2 - 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.
AB - 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.
KW - Drug resistance
KW - Gemcitabine
KW - Micro-array
KW - Ribonucleotide reductase
UR - http://www.scopus.com/inward/record.url?scp=33750440839&partnerID=8YFLogxK
U2 - https://doi.org/10.1080/15257770600890269
DO - https://doi.org/10.1080/15257770600890269
M3 - Article
C2 - 17065054
SN - 1525-7770
VL - 25
SP - 1001
EP - 1007
JO - Nucleosides, Nucleotides and Nucleic Acids
JF - Nucleosides, Nucleotides and Nucleic Acids
IS - 9-11
ER -