Induction of thymidine phosphorylase by interferon and taxanes occurs only in human cancer cells with low thymidine phosphorylase activity.
Induction of thymidine phosphorylase by interferon and taxanes occurs only in human cancer cells with low thymidine phosphorylase activity.
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干扰素和紫杉烷类药物诱导胸苷磷酸化酶仅发生在胸苷磷酸化酶活性较低的人类癌细胞中。
DOI：
10.1016/s0304-3835(02)00358-0
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发表时间：
2002
期刊：
影响因子：
9.7
通讯作者：
R. Hirayama
中科院分区：
文献类型：
--
作者：
M. Fukushima;H. Okabe;T. Takechi;W. Ichikawa;R. Hirayama
胸苷磷酸化酶（TP）调节细胞内胸苷代谢。据报道，它是肿瘤血管生成的预后因子，并激活5-氟尿嘧啶（5-FU）的一些前药成为5-FU。也有证据表明，TP是由干扰素（IFN）和外源性物质，如环磷酰胺和紫杉烷，在实验人类癌细胞和异种移植诱导。我们研究了IFNα和Paclitaxel在体外和体内对低和高TP活性的人肿瘤细胞中TP表达的诱导作用。在TP活性低的KB、NUGC-3和KOC 2S细胞中，IFNα使TP活性增加2 - 4倍，但仍低于未处理的TP活性高的SHIN-3和HRA细胞。IFNα不能促进SHIN-3和HRA细胞的TP活性，但在所有测试的细胞中，TP mRNA的表达响应于IFNα而增加2至4倍。这些结果表明，在IFN诱导TP mRNA扩增后，TP蛋白的表达可能受到另一种因子的转录后调节。与未治疗的肿瘤相比，对KB和KM 20 C肿瘤异种移植的裸鼠单次剂量的Paclitinib表达低TP活性，使TP活性增加约4至7倍。相比之下，MX-1和H-31肿瘤中的TP表达最初很高，并且在紫杉醇治疗后没有改变。所有肿瘤的尿苷磷酸化酶活性在IFNα或Paclitaxel的作用下均无变化。我们测定了干扰素诱导的TP基因转录因子STAT 1 α的水平，发现在低表达TP的肿瘤细胞中，STAT 1 α的水平较低，而在IFN作用下，STAT 1 α的水平显著增加，约为4倍，几乎达到了IFN作用下STAT 1 α水平不变的高表达TP的肿瘤细胞的水平。当同时测量临床切除的结直肠癌中TP活性和STAT 1 α表达时，几乎所有肿瘤都具有TP和STAT 1 α的高表达。总之，我们的研究结果表明，IFN和Paclitaxel影响TP活性低的人癌细胞，但不影响TP活性高的人癌细胞，STAT 1 α表达可能反映TP活性，至少在实验性人癌细胞中是这样。
Thymidine phosphorylase (TP) regulates intracellular thymidine metabolism. It has been reported to be a prognostic factor for tumor angiogenesis and to activate some prodrugs of 5-fluorouracil (5-FU) to 5-FU. There is also evidence that TP is induced by interferons (IFNs) and xenobiotics, such as cyclophosphamide and taxanes, in experimental human cancer cells and xenografts. We investigated the induction of TP expression by IFNα and Paclitaxel in vitro and in vivo in human tumor cells with low and with high TP activity. TP activity in KB, NUGC-3, and KOC2S cells, which had low TP activity, was increased 2 to 4 fold by IFNα, but was still lower than in non-treated SHIN-3 and HRA cells, which have high TP activity. IFNα did not promote TP activity in SHIN-3 and HRA cells, but expression of TP mRNA increased 2 to 4 fold in response to IFNα in all cells tested. These results suggest that the expression of TP protein would be regulated post-transcriptionally by another factor after IFN-induced amplification of TP mRNA. A single dose of Paclitaxel to nude mice xenografted with KB and KM20C tumors, expressing low TP activity, increased TP activity about 4 to 7 fold compared to non-treated tumors. In contrast, TP expression in MX-1 and H-31 tumors was originally high and did not change by the treatment of Paclitaxel. The activities of uridine phosphorylase in all tumors used showed no changes in response to IFNα or Paclitaxel. We determined the level of STAT1α, an IFN-inducible transcription factor of the TP gene, and found that it was low in low TP expressing tumor cells and markedly increased to about 4 fold by IFN, almost reaching the level in high TP expressing cells whose STAT1α level was unchanged by IFN. When TP activity and STAT1α expression in clinically resected colorectal cancers were simultaneously measured, almost all tumors had high expression of both TP and STAT1α. In conclusion, our results suggest that IFN and Paclitaxel affect human cancer cells with low TP activity but not those with high TP activity and that the STAT1α expression may reflect TP activity, at least in experimental human cancer cells.
影响因子：
8.8
作者：
Patterson, A V;Zhang, H;Moghaddam, A;Bicknell, R;Talbot, D C;Stratford, I J;Harris, A L
通讯作者：
Harris, A L
人结肠癌细胞中胸苷磷酸化酶/血小板源性内皮细胞生长因子表达的调节。
影响因子：
11.2
作者：
Schwartz,EL;Wan,E;Wang,FS;Baptiste,N
通讯作者：
Baptiste,N