Expression of transduced tropomyosin 1 cDNA suppresses neoplastic growth of cells transformed by the ras oncogene.

Expression of transduced tropomyosin 1 cDNA suppresses neoplastic growth of cells transformed by the ras oncogene.
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转导的原肌球蛋白 1 cDNA 的表达可抑制 ras 癌基因转化的细胞的肿瘤生长。

DOI:
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发表时间:
1993
影响因子:
11.1
通讯作者:
Herbert L. Cooper
Herbert L. Cooper
中科院分区:
综合性期刊1区
文献类型:
--
作者:
G. L. Prasad;Rebecca A. Fuldner;Herbert L. Cooper

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在被许多逆转录病毒癌基因、转化生长因子α和化学诱变剂肿瘤性转化的成纤维细胞中,微丝相关蛋白原肌球蛋白家族的某些成员的合成受到抑制。为了测试原肌球蛋白抑制是否是肿瘤转化中必需的事件,通过逆转录病毒介导的cDNA转移恢复了被ras癌基因转化的NIH 3T3小鼠细胞中两种被抑制的原肌球蛋白之一的表达。表达插入的 cDNA 的细胞表现出微丝束形成的部分恢复(这在转化细胞中通常是紊乱的)以及细胞质扩散的增加​​。更重要的是,它们失去了不依赖贴壁的生长能力,无胸腺小鼠肿瘤生长的开始被推迟。当肿瘤出现时,它们不再表达插入的 cDNA。这些观察结果支持以下结论:原肌球蛋白抑制是转化表型成分表达的必要事件,特别是对于锚定非依赖性生长和肿瘤发生而言,这与肿瘤潜能密切相关。这种潜在的可逆要求可能会将各种致癌方式产生的不同初始事件与导致肿瘤生长的共同途径联系起来。
Synthesis of certain members of the tropomyosin family of microfilament-associated proteins is suppressed in fibroblasts neoplastically transformed by a number of retroviral oncogenes, by transforming growth factor alpha, and by chemical mutagens. To test whether tropomyosin suppression is a required event in neoplastic transformation, expression of one of two suppressed tropomyosins in NIH 3T3 mouse cells transformed by the ras oncogene was restored by retrovirally mediated cDNA transfer. Cells expressing the inserted cDNA showed partial restoration of microfilament bundle formation (which is typically deranged in transformed cells) together with increased cytoplasmic spreading. More importantly, they lost anchorage-independent growth capability, and the onset of tumor growth in athymic mice was delayed. When tumors arose they no longer expressed the inserted cDNA. These observations support the conclusion that tropomyosin suppression is a necessary event for the expression of components of the transformed phenotype, particularly with respect to anchorage-independent growth and tumorigenesis, which correlate closely with neoplastic potential. This potentially reversible requirement may link different initial events produced by a variety of oncogenic modalities to a common pathway leading to neoplastic growth.
致瘤性人成纤维细胞中原肌球蛋白异构体的转换。
DOI: 10.1128/mcb.6.7.2721-2726.1986
发表时间: 1986
影响因子: 5.3
作者:
Leavitt,J;Latter,G;Lutomski,L;Goldstein,D;Burbeck,S
通讯作者: Burbeck,S