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Dihydrofolate reductase gene amplification-associated shift of differentiation in methotrexate-adapted HT-29 cells.甲氨蝶呤适应的HT-29细胞中,二氢叶酸还原酶基因扩增相关的分化转变
J Cell Biol. 1991 Dec;115(5):1409-18. doi: 10.1083/jcb.115.5.1409.
2
Growth adaptation to methotrexate of HT-29 human colon carcinoma cells is associated with their ability to differentiate into columnar absorptive and mucus-secreting cells.HT-29人结肠癌细胞对甲氨蝶呤的生长适应性与其分化为柱状吸收细胞和黏液分泌细胞的能力有关。
Cancer Res. 1990 Oct 1;50(19):6334-43.
3
Adaptation to 5-fluorouracil of the heterogeneous human colon tumor cell line HT-29 results in the selection of cells committed to differentiation.人结肠肿瘤异质细胞系HT - 29对5 - 氟尿嘧啶的适应性导致了致力于分化的细胞的选择。
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4
Properties of an altered dihydrofolate reductase encoded by amplified genes in cultured mouse fibroblasts.培养的小鼠成纤维细胞中扩增基因编码的改变的二氢叶酸还原酶的特性
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5
Amplified dihydrofolate reductase genes in unstably methotrexate-resistant cells are associated with double minute chromosomes.在不稳定的甲氨蝶呤抗性细胞中扩增的二氢叶酸还原酶基因与双微体染色体相关。
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The use of a fluorescent methotrexate probe to monitor the effects of three vinca alkaloids on a mixed population of parental L1210 and gene-amplified methotrexate-resistant cells by flow cytometry.使用荧光甲氨蝶呤探针,通过流式细胞术监测三种长春花生物碱对亲本L1210和基因扩增的甲氨蝶呤耐药细胞混合群体的影响。
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Protein expression profiles of intestinal epithelial co-cultures: effect of functionalised carbon nanotube exposure.肠道上皮共培养物的蛋白质表达谱:功能化碳纳米管暴露的影响。
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Development of a serum-free co-culture of human intestinal epithelium cell-lines (Caco-2/HT29-5M21).人肠上皮细胞系(Caco-2/HT29-5M21)无血清共培养体系的建立。
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10
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本文引用的文献

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STUDIES ON THE INHIBITION OF DIHYDROFOLATE REDUCTASE BY THE FOLATE ANTAGONISTS.叶酸拮抗剂对二氢叶酸还原酶抑制作用的研究。
J Biol Chem. 1964 Feb;239:479-85.
2
Intronless human dihydrofolate reductase genes are derived from processed RNA molecules.
Proc Natl Acad Sci U S A. 1982 Dec;79(23):7435-9. doi: 10.1073/pnas.79.23.7435.
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A mechanism of resistance to methotrexate. NADPH but not NADH stimulation of methotrexate binding to dihydrofolate reductase.一种对甲氨蝶呤的耐药机制。NADPH而非NADH刺激甲氨蝶呤与二氢叶酸还原酶的结合。
Biochem Pharmacol. 1983 Jun 15;32(12):1837-41. doi: 10.1016/0006-2952(83)90047-3.
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Emergence of permanently differentiated cell clones in a human colonic cancer cell line in culture after treatment with sodium butyrate.丁酸钠处理后,人结肠癌细胞系在培养中出现永久分化的细胞克隆。
Cancer Res. 1984 Sep;44(9):3961-9.
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Amplification and organization of dihydrofolate reductase genes in a human leukemic cell line, K-562, resistant to methotrexate.在对甲氨蝶呤耐药的人白血病细胞系K-562中,二氢叶酸还原酶基因的扩增与组织。
Biochemistry. 1983 Dec 6;22(25):5774-81. doi: 10.1021/bi00294a015.
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Epithelial properties of human colonic carcinoma cell line Caco-2: electrical parameters.人结肠癌细胞系Caco-2的上皮特性:电参数
Am J Physiol. 1984 Sep;247(3 Pt 1):C260-7. doi: 10.1152/ajpcell.1984.247.3.C260.
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Gene amplification in cultured animal cells.培养动物细胞中的基因扩增。
Cell. 1984 Jul;37(3):705-13. doi: 10.1016/0092-8674(84)90406-9.
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The pharmacology and clinical use of methotrexate.甲氨蝶呤的药理学与临床应用。
N Engl J Med. 1983 Nov 3;309(18):1094-104. doi: 10.1056/NEJM198311033091805.
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Chromosomal organization of the human dihydrofolate reductase genes: dispersion, selective amplification, and a novel form of polymorphism.
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10
Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. V. Unitarian Theory of the origin of the four epithelial cell types.小鼠小肠中四种主要上皮细胞类型的起源、分化和更新。V. 四种上皮细胞类型起源的统一理论。
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甲氨蝶呤适应的HT-29细胞中,二氢叶酸还原酶基因扩增相关的分化转变

Dihydrofolate reductase gene amplification-associated shift of differentiation in methotrexate-adapted HT-29 cells.

作者信息

Lesuffleur T, Barbat A, Luccioni C, Beaumatin J, Clair M, Kornowski A, Dussaulx E, Dutrillaux B, Zweibaum A

机构信息

Unité de Recherches sur la Différenciation Cellulaire Intestinale, INSERM U178, Villejuif, France.

出版信息

J Cell Biol. 1991 Dec;115(5):1409-18. doi: 10.1083/jcb.115.5.1409.

DOI:10.1083/jcb.115.5.1409
PMID:1955481
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2289245/
Abstract

Postconfluent cultures of HT-29 cells form a heterogeneous multilayer of which greater than 95% of the cells are undifferentiated. In contrast, when stably adapted to normally lethal concentrations of methotrexate (10(-6)-10(-5) M), they form a monolayer of gobletlike cells (Lesuffleur et al., 1990) which secrete large quantities of mucins and display a discrete brush border with the presence of villin, dipeptidylpeptidase-IV, and carcinoembryonic antigen. When adapted to even higher concentrations of methotrexate (10(-4) and 10(-3) M) there is a shift in the pattern of differentiation from gobletlike to dome-forming absorptive-like cells. These cells still display an apical brush border which expresses villin and dipeptidylpeptidase-IV, but no longer express significant levels of mucins and carcinoembryonic antigen. This shift of differentiation coincides with a sudden amplification of the gene coding for dihydrofolate reductase and an increased activity of the enzyme.

摘要

HT - 29细胞汇合后培养形成异质多层结构,其中超过95%的细胞未分化。相比之下,当稳定适应正常致死浓度的甲氨蝶呤(10^(-6)-10^(-5) M)时,它们形成单层杯状细胞(勒叙弗勒等人,1990年),这些细胞分泌大量粘蛋白,并呈现出含有绒毛蛋白、二肽基肽酶-IV和癌胚抗原的离散刷状缘。当适应更高浓度的甲氨蝶呤(10^(-4)和10^(-3) M)时,分化模式从杯状细胞转变为形成穹顶的吸收样细胞。这些细胞仍然显示出表达绒毛蛋白和二肽基肽酶-IV的顶端刷状缘,但不再表达大量的粘蛋白和癌胚抗原。这种分化转变与编码二氢叶酸还原酶的基因突然扩增以及该酶活性增加相吻合。