Suppression of the malignant phenotype of melanoma cells by anti-oncogene ribozymes.

Suppression of the malignant phenotype of melanoma cells by anti-oncogene ribozymes.
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通过抗癌基因核酶抑制黑色素瘤细胞的恶性表型。

DOI:
10.1111/1523-1747.ep12340688
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发表时间:
1996
期刊:
The Journal of investigative dermatology
影响因子:
--
通讯作者:
Scanlon,KJ
Scanlon,KJ
中科院分区:
--
文献类型:
--
作者:
Ohta,Y;Kijima,H;Kashani-Sabet,M;Scanlon,KJ

文献摘要

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细胞癌基因突变或过表达激活信号转导通路与肿瘤转化有关。在这项研究中,我们提出了针对激活的H-ras癌基因以及针对核原癌基因c-fosand c-mycin的含H-ras突变的FEM人黑色素瘤细胞系的核酶的治疗潜力。转染抗ras核酶的FEM细胞显示具有最长的倍增时间,最少的DNA合成,和最少的菌落在软琼脂中相比,与转染核酶对c-fosor c-mycmRNA。此外,抗rasribozyme克隆在单层培养中表现出与增强的黑色素合成相关的树突状外观。这些结果表明,抗ras核酶不仅可以影响体外培养的人黑色素瘤细胞的增殖,而且可以影响其分化过程。它们还加强了抗癌基因核酶作为黑色素瘤细胞的肿瘤表型抑制因子的作用。
The activation of signal transduction pathways by mutation or overexpression of cellular oncogenes has been associated with neoplastic transformation. In this study, we addressed the therapeutic potential of ribozymes targeted against the activated H-rasoncogene as well as against the nuclear proto-oncogenes c-fosand c-mycin the FEM human melanoma cell line containing a H-rasmutation. FEM cells transfected with the anti-rasribozyme were shown to have the longest doubling time, the least DNA synthesis, and the fewest colonies in soft agar when compared with transfectants with ribozymes against c-fosor c-mycmRNA. Furthermore, anti-rasribozyme clones showed a dendritic appearance in monolayer culture that was associated with enhanced melanin synthesis. These results suggest that the anti-rasribozyme could affect not only the proliferation but also the differentiation process of human melanoma cellsin vitro. They also reinforce the role of anti-oncogene ribozymes as suppressors of the neoplastic phenotype of melanoma cells.