Relationships between heparanase activity and increasing metastatic potential of fibroblasts transfected with various oncogenes.
Relationships between heparanase activity and increasing metastatic potential of fibroblasts transfected with various oncogenes.
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乙酰肝素酶活性与转染各种癌基因的成纤维细胞转移潜能增加之间的关系。
DOI：
10.1016/0304-3835(90)90101-3
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发表时间：
1990
期刊：
影响因子：
9.7
通讯作者：
Wright,JA
中科院分区：
文献类型：
--
作者：
Schwarz,LC;Inoue,T;Irimura,T;Damen,JE;Greenberg,AH;Wright,JA
我们研究了活化的H-ras和其他转化癌基因对乙酰肝素酶活性的影响。通过凝胶渗透色谱法评估转化体细胞提取物对3 HN-乙酰化-部分N-乙酰化硫酸乙酰肝素的降解。用活化的H-ras癌基因转染的10 T12小鼠胚胎成纤维细胞观察到更广泛的降解。显示具有最高转移潜能的细胞（CIRAS-3）含有最大的乙酰肝素酶活性，其活性水平比亲本细胞高49%（P< 0.0002）。此外，由一系列H-ras转化细胞系产生的酶活性随着转移潜能而逐渐增加（非参数秩相关系数r= 0.96）。NIH 3 T3成纤维细胞转染活化的H-ras，v-src或v-fes癌基因，诱导转移表型，并没有导致乙酰肝素酶活性的大幅增加。此外，通过共转染大鼠REF细胞与Ad 2 E1 a癌基因来抑制ras诱导的恶性肿瘤并没有产生乙酰肝素酶活性的显著下降。这些结果与以下观点一致，即乙酰肝素酶活性的修饰在某些但不是所有情况下在复杂的转移过程中发挥作用。
We have examined the effects of transformation by activated H-ras and other transforming oncogenes on the activity of the enzyme, heparanase. Degradation of 3 HN-acetylated-partially N-desulfated heparan sulfate by cellular extracts of the transformants was assessed by gel permation chromatography. More extensive degradation was observed with 10T 1 2 mouse embryo fibroblasts transfected with an activated H-ras oncogene. The cells having the highest metastatic potential (CIRAS-3) were shown to contain the greatest heparanase activity, giving 49% higher levels of activity than parental cells (P< 0.0002). Furthermore, the enzyme activity produced by a series of H-ras transformed cell lines increased progressively with metastatic potential (non-parametric rank correlation coefficient r= 0.96). Transfection of NIH 3T3 fibroblasts with activated H-ras, v-src or v-fes oncogenes, which induced the metastatic phenotype, did not lead to large increases in heparanase activities. Also, inhibition of rasinduced malignancy by cotransfection of rat REF cells with the Ad2 E1a oncogene did not produce significant declines in heparanase activities. These results are consistent with the view that modifications in heparanase activity can play a role in the complex process of metastasis in some, but not all situations.