Altered expression of ribonucleotide reductase and role ofM2 gene amplification in hydroxyurea-resistant hamster, mouse, rat, and human cell lines
Altered expression of ribonucleotide reductase and role ofM2 gene amplification in hydroxyurea-resistant hamster, mouse, rat, and human cell lines
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羟基脲抗性仓鼠、小鼠、大鼠和人类细胞系中核糖核苷酸还原酶表达的改变和 M2 基因扩增的作用
DOI：
10.1007/bf01534695
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
L. Thelander
中科院分区：
文献类型：
--
作者：
J. Wright;Tawfiq G. Alam;G. McClarty;A. Tagger;L. Thelander
已经表征了对羟基脲的细胞毒性作用具有抗性的五种仓鼠、小鼠和大鼠细胞系。所有细胞系均含有增加的核糖核苷酸还原酶活性，通过电子顺磁共振光谱法判断核糖核苷酸还原酶的M2组分水平升高，通过北方印迹分析测定M2 mRNA拷贝增加。在啮齿动物细胞系中检测到两种M2 mRNA，仓鼠和大鼠细胞中约3.4 kb的高分子量物质，小鼠细胞中约2.1 kb。低分子量M2 mRNA在所有啮齿动物系中约为1.6 kb。北方印迹分析表明，核糖核苷酸还原酶的另一个组成部分，M1，在耐药细胞中没有显着升高，并存在作为一个单一的3.1 kb的物种。5个抗性品系中有4个含有M2基因扩增，这一点通过Southern印迹分析确定，为支持早期的建议提供了直接证据，即羟基脲抗性通常伴随着核糖核苷酸还原酶基因的扩增。即使在仅表现出适度耐药性的细胞中也检测到基因剂量的增加。与耐药啮齿类动物系的观察结果一致，还发现对羟基脲耐药的人（HeLa）细胞系中两种M2 mRNA种类（约3.4和1.6 kb）的水平增加，并表现出M2基因扩增。一种仓鼠细胞系在细胞特征方面与其他耐药啮齿动物系相似，但未显示M1或M2基因扩增，这提供了一个耐药机制的实例，其中M2 mRNA升高，而M2基因拷贝数未伴随增加。
Five hamster, mouse, and rat cell lines resistant to the cytotoxic effects of hydroxyurea have been characterized. All cell lines contained increased ribonucleotide reductase activity, elevated levels of the M2 component of ribonucleotide reductase as judged by electron paramagnetic resonance spectroscopy, and increased copies of M2 mRNA as determined by Northern blot analysis. Two species of M2 mRNA were detected in rodent cell lines, a high-molecular-weight species of approximately 3.4 kb in hamster and rat cells and about 2.1 kb in mouse cells. The low molecular-weight M2 mRNA was about 1.6 kb in all rodent lines. Northern blot analysis showed that the mRNA for the other component of ribonucleotide reductase, M1, was not markedly elevated in the drug-resistant cells and existed as a single 3.1-kb species. Four of the five resistant lines contained an M2gene amplification as determined by Southern blot analysis, providing direct evidence to support earlier suggestions that hydroxyurea resistance is often accompanied by amplification of a ribonucleotide reductase gene. An increase in gene dosage was detected even in cells exhibiting only modest drug-resistance properties. No evidence for amplification of the M1gene of ribonucleotide reductase was found. In keeping with these observations with drug-resistant rodent lines, a human (HeLa) cell line resistant to hydroxyurea was also found to contain increased levels of two M2 mRNA species (about 3.4 and 1.6 kb) and exhibited M2gene amplification. One hamster cell line resembled the other resistant rodent lines in cellular characteristics but did not show amplification of either the M1or M2gene, providing an example of a drug-resistant mechanism in which an elevation of M2 mRNA has occurred without a concomitant increase in M2gene copy number.
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基因扩增、耐药性和癌症。
影响因子：
11.2
作者：
Schimke,RT
通讯作者：
Schimke,RT
影响因子：
13.5
作者：
John R. Riordan;Victor Ling
通讯作者：
John R. Riordan;Victor Ling
精氨基琥珀酸合成酶 mRNA cDNA 的克隆以及人类细胞系中酶过量生产的研究。
DOI：
--
发表时间：
1981
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Su,TS;Bock,HG;O'Brien,WE;Beaudet,AL
通讯作者：
Beaudet,AL
人核糖核苷酸还原酶 M1 亚基的结构基因分配到 11 号染色体的短臂。
影响因子：
3.7
作者：
Engström,Y;Francke,U
通讯作者：
Francke,U
对响应 2,3,7,8-四氯二苯并-对二恶英过度转录细胞色素 P1-450 基因的变异小鼠肝癌细胞进行生化和遗传分析。
DOI：
--
发表时间：
1984
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Jones,PB;Miller,AG;Israel,DI;Galeazzi,DR;WhitlockJr,JP
通讯作者：
WhitlockJr,JP