The Relationship of Arginine Deprivation, Argininosuccinate Synthetase and Cell Death in Melanoma
The Relationship of Arginine Deprivation, Argininosuccinate Synthetase and Cell Death in Melanoma
复制标题
黑色素瘤精氨酸剥夺、精氨基琥珀酸合成酶与细胞死亡的关系
作者：
N. Savaraj;Chunjing Wu;M. Kuo;M. You;M. Wangpaichitr;C. Robles;S. Spector;L. Feun
研究表明，黑色素瘤细胞不表达氨基琥珀酸合成酶（ASS），因此不能从瓜氨酸合成精氨酸。使用聚乙二醇化精氨酸脱亚胺酶（ADI-PEG 20）消耗精氨酸导致黑色素瘤中的细胞死亡，而不是正常细胞。这一概念被转化为临床试验，并看到了反应。然而，ASS表达的诱导确实发生，这导致对ADI-PEG 20的抗性。我们使用了4个黑色素瘤细胞系来研究可能支配ASS表达的因素。虽然这4种黑色素瘤细胞系不表达ASS蛋白或mRNA，如通过免疫印迹和northernblot分析所检测到的，但ASS蛋白在这些细胞在ADI-PEG 20存在下生长后可以被诱导，但在培养基中补充精氨酸后再次被抑制。诱导水平不同，一个细胞系无法诱导。有趣的是，具有最高诱导水平的黑素瘤细胞系也可以对ADI-PEG 20产生抗性。该抗性系具有高水平的ASS mRNA和蛋白质表达，其不能被精氨酸抑制。我们的研究表明，ASS在黑色素瘤细胞中的表达是复杂的，并受到黑色素瘤细胞之间不同的生化参数的控制。
It has been shown that melanoma cells do not express argininosuccinate synthetase (ASS) and therefore are unable to synthesize arginine from citrulline. Depleting arginine using pegylated arginine deiminase (ADI-PEG20) results in cell death in melanoma but not normal cells. This concept was translated into clinical trial and responses were seen. However, induction of ASS expression does occur which results in resistance to ADI-PEG20. We have used 4 melanoma cell lines to study factors which may govern ASS expression. Although these 4 melanoma cell lines do not express ASS protein or mRNA as detected by both immunoblot and northernblot analysis, ASS protein can be induced after these cells are grown in the presence of ADI-PEG20, but again repressed after replenishing arginine in the media. The levels of induction are different and one cell line could not be induced. Interestingly, a melanoma cell line with the highest level of induction could also be made resistant to ADI-PEG20. This resistant line possesses high levels of ASS mRNA and protein expression which cannot be repressed with arginine. Our study indicates that ASS expression in melanoma cells is complex and governed by biochemical parameters which are different among melanoma cells.
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：
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发表时间：
1981
期刊：
The Journal of biological chemistry
影响因子：
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作者：
Su,TS;Bock,HG;O'Brien,WE;Beaudet,AL
通讯作者：
Beaudet,AL