Thymidylate synthase dihydropyrimidine dehydrogenase and thymidine phosphorylase expression in colorectal cancer and normal mucosa in patients

Thymidylate synthase dihydropyrimidine dehydrogenase and thymidine phosphorylase expression in colorectal cancer and normal mucosa in patients
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DOI:
10.1097/01.fpc.0000230410.07899.bc
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发表时间:
2006-11-01
影响因子:
2.6
通讯作者:
Danesi, Romano
Danesi, Romano
中科院分区:
医学4区
文献类型:
--
作者:
Amatori, Federica;Di Paolo, Antonello;Danesi, Romano

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目的 比较胸苷酸合酶(TS)、二氢嘧啶脱氢酶(DPD)和胸苷磷酸化酶(TP)基因多态性及在初治结直肠癌(CRC)和正常黏膜中的表达情况。方法采用实时逆转录聚合酶链反应分析53例3-磷酸甘油醛脱氢酶患者原发性CRC及癌旁正常组织中TS、DPD和TP mRNA的表达情况。作为看家基因。通过聚合酶链反应和限制性片段长度多态性测定来确定 TS 启动子(TSER 和 C/G SNP)和 DPD IVS14 + 1G > A 基因型。此外,在Colo 320、HT-29、CaCo-2和SW620人CRC细胞系中评估了TS、DPD和TP表达与5-氟尿嘧啶细胞毒性之间的相关性。结果TP和DPD mRNA表达在肿瘤和正常组织中存在显着差异(751 +/- 13.50 vs. 1.10 +/- 0.57,P < 0.05和0.60 +/- 0.63 与 1.17 +/- 0.55,P
Objective To compare thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and thymidine phosphorylase (TP) gene polymorphism and expression in colorectal cancer (CRC), and normal mucosa in chemotherapy-naive patients.Methods TS, DPD and TP mRNA expression was analysed by real-time reverse-transcription polymerase chain reaction in primary CRC and adjacent normal tissues from 53 patients with glyceraidehyde-3-phosphate dehydrogenase as housekeeping gene. TS promoter (TSER and C/G SNP) and DPD IVS14 + 1G > A genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism assays. Moreover, the correlation between TS, DPD and TP expression and cytotoxicity of 5-fluorouracil was evaluated in Colo 320, HT-29, CaCo-2 and SW620 human CRC cell lines.Results TP and DPD mRNA expression was significantly different in tumour and normal tissue (751 +/- 13.50 vs. 1.10 +/- 0.57, P < 0.05 and 0.60 +/- 0.63 vs. 1.17 +/- 0.55, P