[Correlation between enzymatic activity and gene expression of orotate phosphoribosyl transferase (OPRT) in colorectal cancer].
[Correlation between enzymatic activity and gene expression of orotate phosphoribosyl transferase (OPRT) in colorectal cancer].
复制标题
结直肠癌乳清酸磷酸核糖转移酶（OPRT）酶活性与基因表达的相关性
DOI：
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发表时间：
2002
期刊：
影响因子：
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通讯作者：
I. Nagaoka
中科院分区：
文献类型：
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作者：
Ochiai Takumi;Sugitani Michiharu;Nishi Kazuhiko;N. Hajime;Okada Tsuyoshi;Suda Sumito;Kamiyama Hirohiko;I. Nagaoka
背景
乳清酸磷酸核糖转移酶（OPRT）是5-FU代谢途径的起始关键酶。它是一种将5-氟尿嘧啶转化为5-氟尿苷一磷酸的酶。我们以前已经表明，有一个强的正相关性OPRT活性和5-FU的抗肿瘤作用。在这项研究中，我们研究了OPRT活性和OPRT mRNA表达水平之间的相关性在10个结直肠肿瘤。
方法
通过组织中的放射性测定来测量活性。通过TaqMan PCR测定在相同组织中测量mRNA表达水平（OPRT/β-肌动蛋白）。
结果
OPRT活性与mRNA表达水平无相关性（r =-0.4301，p = 0.8926）。
讨论
酶的绝对量由合成速度（kappa s）和降解速度（kappa deg）决定。OPRT被认为是一种组成型酶，本研究的结果表明，很难从mRNA表达水平估计OPRT活性。
结论
有必要进一步研究开发技术来测量活检组织中的OPRT活性，以便根据OPRT（一种与5-FU代谢相关的酶）估计5-FU的抗肿瘤作用来建立量身定制的疗法。
BACKGROUND
Orotate phosphoribosyl transferase (OPRT) is the initial key enzyme in the 5-FU metabolic pathway. It is an enzyme that converts 5-fluorouracil into 5-fluorouridine monophosphate. We have previously shown that there is a strong positive correlation between OPRT activity and the antitumor effects of 5-FU. In this study, we investigated the correlation between OPRT activity and mRNA expression levels of OPRT in 10 colorectal tumors.
METHODS
Activity was measured by radioassay in tissues. mRNA expression levels (OPRT/beta-actin) were measured by TaqMan PCR assay in the same tissues.
RESULTS
There was no correlation between OPRT activity and mRNA expression levels (r = -0.4301, p = 0.8926).
DISCUSSION
The absolute amount of an enzyme is determined by speed of synthesis (kappa s) and degradation (kappa deg). OPRT is thought to be a constitutive enzyme, and the results of this study show that it is difficult to estimate the OPRT activity from mRNA expression levels.
CONCLUSIONS
Further studies are necessary to develop techniques to measure OPRT activity in biopsies, in order to establish tailor-made therapies based on estimating the antitumor effect of 5-FU from OPRT, an enzyme related to 5-FU metabolism.