Analysis of single nucleotide polymorphisms in uridine/cytidine kinase gene encoding metabolic enzyme of 3′-ethynylcytidine
2002
SUMMARY We investigated single nucleotide polymorphisms (SNPs) in uck2 gene encoding metabolic enzyme of 3'-ethynylcyt idine (ECyd) which were associated with drug response of ECyd, and the newly synthesized antitumor ribonucleoside analog. We analized that on exon-intron junction and exon region to affect the qualitative alteration of gene product directly in ECyd sensitive and resistant human cancer cell lines. As the results, cSNP and sSNP were detected in exon 4. In the promoter region, 3 SNPs were detected. Our data seem to be able to give an important knowledge, when ECyd is applied clinically. the activation or result which any of UCK1 and UCK2 is concerned in the activation. UCK2 mRNA was investigated using the Real Time PCR in ECyd sensitive and ECyd resistant cell from human cancer. In the ECyd resistant cells, mRNA levels of UCK2 were lower than that of ECyd sensitive cells. Therefore, it was clear that UCK2 was directly concerned in the metabolic activation of ECyd. In this study, we analyzed SNPs of uck2 gene which encoded metabolic activation enzyme of ECyd in ECyd sensitive and resistant human cancer cell lines. Our data show an correlation of SNPs with the drug responsibility an important knowledge when ECyd will applied for cancer chemotherapy.
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