Associations between gene polymorphisms of thymidylate synthase with its protein expression and chemosensitivity to 5-fluorouracil in pancreatic carcinoma cells
Associations between gene polymorphisms of thymidylate synthase with its protein expression and chemosensitivity to 5-fluorouracil in pancreatic carcinoma ceils作者机构：Department of General Surgery Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100730 China
出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)
年 卷 期：2011年第124卷第2期
页 面：262-267页
核心收录：
学科分类：1007[医学-药学(可授医学、理学学位)] 07[理学] 0713[理学-生态学] 10[医学]
主 题：thymidylate synthase gene polymorphisms pancreatic carcinoma
摘 要：Background Thymidylate synthase （TS） is a key regulatory enzyme for de novo DNA *** activity is also an important determinant of the response to chemotherapy with fluoropyrimidine prodrugs,and its expression may be affected by gene *** this study,we investigated the associations between polymorphisms of the TS gene and its protein expression,and the implications on the efficacy of 5-fluorouracil （5-FU） in pancreatic cancer *** Genotypes based on the 28-bp TS tandem repeat for pancreatic cell lines were determined by electrophoretic analysis of PCR products.A single nucleotide polymorphism （SNP） at nucleotide 12 of the second 28-bp repeat of the 3R allele was determined by nucleotide *** chemosensitivity of pancreatic carcinoma cells to 5-FU in vitro was evaluated using Cell Counting Kit-8 （CCK-8）.TS protein expression was analyzed by Western *** Seven pancreatic carcinoma cell lines had different genotypes in terms of the 28-bp TS tandem repeat,as follows：homozygous 2R/2R （T3M4 and BxPC-3 cells）,heterozygous 2R/3R （AsPC-1,Capan-1,and SU86.86）,and homozygous 3R/3R （PANC-1 and COLO357）.The optical density ratio of genotypes 3R/3R,2R/2R and 2R/3R was 1.393±0.374,0.568±0.032 and 0.561±0.056,*** with the 2R/3R or 3R/3R genotypes were further analyzed for the G to C SNP at nucleotide 12 of the second 28-bp repeat of the 3R allele,yielding heterozygous 2R/3Rc （AsPC-1,Capan-1,and SU86.86）,homozygous 3Rg/3Rg （COLO357） and homozygous 3Rc/3Rc （PANC-1）.The optical density ratio of homozygous 3Rg/3Rg cells and homozygous 3Rc/3Rc cells was 1.723±0.062 and 1.063±0.134,respectively,and this difference was statistically significant （P 〈0.05）.Cells with the 2R/2R and 2R/3R genotypes of TS were hypersensitive to 5-FU in vitro as compared with those with the 3R/3R *** Polymorphisms in the TS gene influenced its protein expression and affected sensitivity of 5-FU in seven pancreatic cancer cell ***
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