Reversal of the malignant phenotype by an anti-ras ribozyme.

Reversal of the malignant phenotype by an anti-ras ribozyme.
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抗ras核酶逆转恶性表型。

DOI:
10.1089/ard.1992.2.3
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发表时间:
1992
期刊:
Antisense research and development
影响因子:
--
通讯作者:
Moreno,JG
Moreno,JG
中科院分区:
--
文献类型:
--
作者:
Kashani-Sabet,M;Funato,T;Tone,T;Jiao,L;Wang,W;Yoshida,E;Kashfinn,BI;Shitara,T;Wu,AM;Moreno,JG

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本研究设计了一种核酶(催化RNA),对人膀胱癌EJ细胞中表达的激活的H-ras基因的mRNA进行位点特异性切割。在体外实验中,确定了核酶催化切割的最佳条件。将编码核酶的合成DNA克隆到哺乳动物表达载体(pHβAPr-1)中,并转染到EJ细胞中。表达的核酶显著改变了EJ细胞的形态,抑制了EJ细胞的生长。通过原位(经尿道)植入模型在无胸腺(裸)小鼠中检查这些细胞系的恶性潜能,该模型概括了各种膀胱癌的侵袭潜能。表达H-ras核酶的EJ肿瘤的特征在于与对照EJ细胞形成的肿瘤相比,肿瘤摄取和侵袭显著减少。这些差异导致植入含核酶的EJ细胞的小鼠的存活率几乎增加了两倍。这些结果进一步阐明了ras基因在肿瘤发生和侵袭中的作用,并介绍了核酶作为一类新的抗癌剂。
In this study a ribozyme (catalytic RNA) was designed to site specifically cleave the mRNA of the activated H-rasgene expressed in human bladder carcinoma EJ cells. The optimal conditions for catalytic cleavage by the ribozyme were demonstratedin vitro. A synthetic DNA encoding the ribozyme was cloned into a mammalian expression vector (pHβAPr-1) and transfected into EJ cells. The expressed ribozyme significantly altered the morphology and suppressed the growth of EJ cellsin vitro. These cell lines were examined for their malignant potential in athymic (nude) mice by an orthotopic (transurethral) implantation model, which recapitulates the invasive potential of various bladder carcinomas. EJ tumors expressing the H-rasribozyme were characterized by a marked reduction in tumor take and invasion compared to those formed by control EJ cells. These differences resulted in almost a twofold increase in survival of mice implanted with ribozyme-containing EJ cells. These results further elucidate the role ofrasgenes in tumorigenicity and invasion, as well as introduce ribozymes as a new class of anticancer agents.
DOI: --
发表时间: 1988
期刊: Cancer Research
影响因子: 11.2
作者:
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影响因子: 11.2
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期刊: SCIENCE
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发表时间: 1990-08-24
期刊: SCIENCE
影响因子: 56.9
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发表时间: 1990
影响因子: 5.3
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