Sensitivity of human cancer cells to the new anticancer ribo-nucleoside TAS-106 is correlated with expression of uridine-cytidine kinase 2.
Sensitivity of human cancer cells to the new anticancer ribo-nucleoside TAS-106 is correlated with expression of uridine-cytidine kinase 2.
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DOI：
10.1111/j.1349-7006.2002.tb01325.x
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发表时间：
2002-07
期刊：
影响因子：
--
通讯作者：
Fukushima M
中科院分区：
文献类型：
--
作者：
Shimamoto Y;Koizumi K;Okabe H;Kazuno H;Murakami Y;Nakagawa F;Matsuda A;Sasaki T;Fukushima M
TAS-106 [1-（3-C-乙炔基-β-d-核糖-戊呋喃糖基）胞嘧啶]是一种新型抗癌核糖核苷，具有良好的抗肿瘤活性。我们之前提供的证据表明，细胞对TAS-106的敏感性与TAS-106三磷酸盐的细胞内蓄积相关，这可能受到细胞膜转运机制和尿苷-胞苷激酶（UCK）活性的影响。由于最近在人类细胞中报告了由UCK 1和UCK 2两个成员组成的UCK家族的存在，因此我们在一组10种人类癌细胞系中研究了UCK 1和UCK 2在mRNA和蛋白水平上的表达与UCK活性（TAS-106磷酸化活性）之间的关系。这些细胞系中UCK活性的测量结果显示，其与细胞对TAS-106的敏感性密切相关。UCK 2的mRNA或蛋白表达水平与UCK活性密切相关，而UCK 1的mRNA和蛋白表达水平与酶活性均不相关。因此，我们比较了UCK 2在几种人类肿瘤组织和相应的正常组织中的蛋白表达水平。UCK 2蛋白在5例人肿瘤组织中的4例中几乎检测不到表达，但在胰腺肿瘤组织中倾向于高表达。在任何正常组织中均无法检测到。因此，UCK 2的表达似乎与细胞对TAS-106的敏感性相关，可能有助于TAS-106的肿瘤选择性细胞毒性。
TAS–106 [l–(3–C‐ethynyl‐β‐d‐ribo‐pentofuranosyl)cytosine] is a new anticancer ribo‐nucleoside with promising antitumor activity. We have previously presented evidence suggesting that the TAS–106 sensitivity of cells is correlated with intracellular accumulation of the triphosphate of TAS–106, which may be affected both by cellular membrane transport mechanisms and uridine‐cytidine kinase (UCK) activity. Since the presence of a UCK family consisting of two members, UCK1 and UCK2, has recently been reported in human cells, we investigated the relation between expression of UCK1 and UCK2 at both the mRNA and protein levels and UCK activity (TAS–106 phosphorylation activity) in a panel of 10 human cancer cell lines. Measurement of UCK activity in these cell lines revealed that it was well correlated with the cells' sensitivity to TAS–106. In addition, the mRNA or protein expression level of UCK2 was closely correlated with UCK activity in these cell lines, but neither the level of expression of UCK1 mRNA nor that of protein was correlated with enzyme activity. We therefore compared the protein expression level of UCK2 in several human tumor tissues and the corresponding normal tissues. Expression of UCK2 protein was barely detectable in 4 of the 5 human tumor tissues, but tended to be high in the pancreatic tumor tissue. It could not be detected at all in any of the normal tissues. Thus, expression of UCK2 appeared to be correlated with cellular sensitivity to TAS–106, and it may contribute to the tumor‐selective cytotoxicity of TAS–106.
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影响因子：
5.8
作者：
AHMED, NK;HAGGITT, RC;WELCH, AD
通讯作者：
WELCH, AD
影响因子：
3.6
作者：
Van Rompay, AR;Norda, A;Karlsson, A
通讯作者：
Karlsson, A
影响因子：
1.3
作者：
Graham, KA;Leithoff, J;Cass, CE
通讯作者：
Cass, CE
影响因子：
2.7
作者：
Matsuda, A;Hattori, H;Sasaki, T
通讯作者：
Sasaki, T
DOI：
10.1111/j.1349-7006.2002.tb01276.x
发表时间：
2002-04-01
期刊：
JAPANESE JOURNAL OF CANCER RESEARCH
影响因子：
--
作者：
Shimamoto, Y;Kazuno, H;Fukushima, M
通讯作者：
Fukushima, M