Institute for Innovative Cancer Research, Department of Nuclear Medicine, University of Ulsan College of Medicine, Asan Medical Center, Pungnap 2-dong, Songpa-gu, Seoul 138-736, Korea.
Anticancer Res. 2011 Jun;31(6):2135-9.
Thymidine kinase 1 (TK1) and 5'(3')-deoxyribonucleotidase (dNT1) regulate the metabolism of thymidine and its analogs. However, the expression patterns and roles of these enzymes in fluorothymidine (FLT) uptake have not been systemically studied.
TK1 and dNT1 mRNAs were determined by quantitative PCR in 20 asynchronously growing lung and colon cancer cell lines. [3H]FLT uptake and doubling time were measured.
The TK1/GAPDH values varied from 3.09×10(-3)±6.62×10(-4) to 2.44×10(-2)±8.49×10(-4) and dNT1/GAPDH values from 5.84×10(-4)±4.88×10(-5) to 1.59×10(-2)±1.20×10(-3). The correlation coefficient of TK1/GAPDH versus dNT1/GAPDH was 0.669 (p<0.001). [3H]FLT uptake showed negative moderate correlation with dNT1/GAPDH levels (r=-0.563; p<0.01), but no significance with TK1/GAPDH levels. Doubling time had no relationship with the TK1 or dNT1 expression.
This study profiled correlative expression of TK1 and dNT1 in cancer cell lines, and showed that dNT1 expression determines the lower uptake of FLT, providing a basis for understanding deoxyribonucleotide metabolism.
胸苷激酶 1（TK1）和 5'（3'）-脱氧核苷酸酶（dNT1）调节胸苷及其类似物的代谢。然而，这些酶在氟胸苷（FLT）摄取中的表达模式和作用尚未得到系统研究。
在 20 个不同步生长的肺癌和结肠癌细胞系中，通过定量 PCR 测定 TK1 和 dNT1 mRNA。测量 [3H]FLT 摄取和倍增时间。
TK1/GAPDH 值从 3.09×10(-3)±6.62×10(-4)变化到 2.44×10(-2)±8.49×10(-4)，dNT1/GAPDH 值从 5.84×10(-4)±4.88×10(-5)变化到 1.59×10(-2)±1.20×10(-3)。TK1/GAPDH 与 dNT1/GAPDH 的相关系数为 0.669（p<0.001）。[3H]FLT 摄取与 dNT1/GAPDH 水平呈负中度相关（r=-0.563；p<0.01），但与 TK1/GAPDH 水平无显著相关性。倍增时间与 TK1 或 dNT1 表达无关。
本研究描绘了癌症细胞系中 TK1 和 dNT1 的相关表达，并表明 dNT1 表达决定了 FLT 的摄取较低，为理解脱氧核苷酸代谢提供了依据。
