The role of thymidine phosphorylase in the induction of early growth response protein-1 and thrombospondin-1 by 5-fluorouracil in human cancer carcinoma cells
The role of thymidine phosphorylase in the induction of early growth response protein-1 and thrombospondin-1 by 5-fluorouracil in human cancer carcinoma cells
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DOI：
10.3892/ijo_00000602
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发表时间：
2010-05-01
影响因子：
5.2
通讯作者：
Akiyama, Shin-Ichi
中科院分区：
文献类型：
--
作者：
Matsushita, Shigeto;Ikeda, Ryuji;Akiyama, Shin-Ichi
胸苷磷酸化酶（TP）是一种参与胸苷向胸腺嘧啶可逆转化的酶。TP与血管生成因子相同，血小板源性内皮细胞生长因子（PD-ECGF）和TP在多种恶性肿瘤中的表达水平均高于癌旁非肿瘤组织。5-FU）。用TP cDNA转染人胃癌AZ 521细胞和表皮样癌KB细胞。AZ 521/TP和KB/TP细胞是高表达TP的AZ 521/TP和KB/TP细胞，对5-FU敏感性高于相应的亲本细胞TPI。一种新合成的TP抑制剂（Ki= 2.36 × 10（-9）M）。5-甲酰四氢叶酸（leucovorin：LV）稳定胸苷酸合成碱（TS）和5-氟-脱氧尿苷-单磷酸（HUMP）的复合物。表达TP的AZ 521细胞对5-FU的敏感性增加，但亲代细胞的敏感性没有增加。表达TP的细胞中的FdUMP水平显著高于亲代细胞，TPI显著降低FdUMP至与亲代细胞相当的水平。5-FU增加早期生长反应蛋白-1（Egr-1）和血管生成抑制剂的表达。血小板反应蛋白-1（TSP-1），在KB/TP细胞中，但在KB/CV细胞中仅轻微，如果有TPI，则可减弱5-FU对Egr-1和TSP-1 mRNA的诱导。结果表明，TP在KB/TP细胞中对FdUMP的产生和对5-FU的反应增强起主要作用。和FdUMP，但不是Fun）参与KB细胞中Egr-1和TSP-1的诱导
Thymidine phosphorylase (TP) is an enzyme involved in reversible conversion of thymidine to thymine TP is identical to an angiogenic factor, pletelet-derived endothelial cell growth factor (PD-ECGF) and the expression levels of TP in a variety of malignant tumors were higher than the adjacent non-neoplastic tissues To investigate the molecular basis for the effect of TP on the metabolic process and the anticancer effect of 5-fluorouracil (5-FU). human gastric carcinoma AZ521 cells and epidermoid carcinoma KB cells were transfected with TP cDNA. and AZ521/TP and KB/TP were cloned AZ521/TP and KB/TP cells overexpressed TP and were more sensitive to 5-FU than the counterpart parental cells TPI. a newly synthesized inhibitor for TP (Ki=2 36x10(-9)M). decreased the sensitivity to 5-FU of the TP expressing cells but not of the parental cells 5-Formyltetrahydrofolate (leucovorin: LV) stabilized the complex of thymidylate synt base (TS) and 5-fluoro-deoxyuridine-monophosphate (HUMP). increased the sensitivity to 5-FU of TP expressing AZ521 cells, but not of the parental cells The levels of FdUMP in TP expressing cells were significantly higher than in parental cells and TPI considerably decreased FdUMP to the level comparable to that in the parental cells 5-FU increased the expression of early growth response protein-1 (Egr-1) and an angiogenesis inhibitor. thrombospondin-1 (TSP-1), in KB/TP cells but only slightly in KB/CV cells, if any TPI attenuated the induction of Egr-1 and TSP-1 mRNA by 5-FU. while LV increased the expression of Egr-1 and TSP-1 mRNA in KB/TP cells These findings demonstrate that the TP has a principal role in the production of FdUMP and the enhanced responses to 5-FU by leucovorin in TP-overexpressing KB and AZ521 cells. and FdUMP but not Fun) is implicated in the induction of Egr-1 and TSP-1 in KB cells