Cancer cell sensitivity to arginine deprivation in vitro is not determined by endogenous levels of arginine metabolic enzymes
Cancer cell sensitivity to arginine deprivation in vitro is not determined by endogenous levels of arginine metabolic enzymes
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DOI：
10.1042/cbi20100451
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发表时间：
2010-11-01
影响因子：
3.9
通讯作者：
Stasyk, Oleh V.
中科院分区：
文献类型：
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作者：
Bobak, Yaroslav P.;Vynnytska, Bozhena O.;Stasyk, Oleh V.
单氨基酸精氨酸（Arg）剥夺目前被认为是治疗某些类型肿瘤的治疗方法；肿瘤细胞对Arg限制的敏感性或抗性的分子机制仍然知之甚少。在这里，我们解决了内源性关键精氨酸代谢酶[分解代谢精氨酸酶，ARG1（精氨酸酶1型）和ARG2（精氨酸酶2型），以及合成代谢：鸟氨酸转氨基甲酰基酶OTC（鸟氨酸转氨基甲酰基酶）和精氨酸琥珀酸合成酶ASS)]水平是否影响体外精氨酸剥夺的细胞反应的问题。不同来源的人上皮癌细胞对精氨酸剥夺的敏感性不同，提供了实验模型。所分析的酶的基础表达状态，以及它们在精氨酸戒断后的变化，都与癌细胞对精氨酸剥夺的敏感性无关。然而，利用外源精氨酸前体（鸟氨酸和瓜氨酸）在缺乏精氨酸的培养基中生长的能力与相应酶OTC和ASS的表达密切相关。我们还观察到，在所有类型的肿瘤细胞中，OTC的表达低于检测水平，这表明在体外，至少对它们来说，精氨酸是一种必需氨基酸。
Single amino acid Arg (arginine) deprivation is currently considered as a therapeutic approach to treat certain types of tumours; the molecular mechanisms that underlie tumour cell sensitivity or resistance to Arg restriction are still little understood. Here, we address the question of whether endogenous levels of key Arg metabolic enzymes [catabolic: arginases, ARG1 (arginase type 1) and ARG2 (arginase type 2), and anabolic: OTC (ornithine transcarbamylase) and ASS (argininosuccinate synthetase)] affect cellular responses to arginine deprivation in vitro. Human epithelial cancer cells of different organs of origin exhibiting variable sensitivity to Arg deprivation provided the experimental models. Neither the basal expression status of the analysed enzymes, nor their changes upon arginine withdrawal correlated with cancer cell sensitivity to arginine deprivation. However, the ability to utilize exogenous Arg precursors (ornithine and citrulline) for growth in Arg-deficient medium strongly correlated with expression of the corresponding enzymes, OTC and ASS. We also observed that OTC expression was below the level of detection in all the types of tumour cells analysed, suggesting that in vitro, at least for them, Arg is an essential amino acid.