SV40-mediated transformation and immortalization of human cells.

SV40-mediated transformation and immortalization of human cells.
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发表时间:
1998
期刊:
Developments in biological standardization
影响因子:
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通讯作者:
S. H. Kim;S. Banga;K. Jha;H. Ozer
S. H. Kim;S. Banga;K. Jha;H. Ozer
中科院分区:
其他
文献类型:
--
作者:
S. H. Kim;S. Banga;K. Jha;H. Ozer

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SV40 感染人类细胞会导致转化和裂解感染。我们使用了起源缺陷型病毒突变体,这些突变体无法在允许的细胞中复制,以帮助分析转化。大 T 抗原 (T ag) 和小 t 抗原的表达导致其他物种转化特征的生长表型改变。人类二倍体成纤维细胞(HF)的寿命有限并且会衰老;标签可以延长寿命,但只有在极少数情况下,细胞才能持续生长并且永生。我们开发了一套匹配的非永生化和永生化转化 HF,用于评估永生化所需的步骤。总结结果以表征 T 依赖性和 T 独立功能。已鉴定出一种新的生长抑制基因 SEN6,其失活是永生化所必需的;它还可以作为标记来区分 SV40 正在复制的细胞和负责肿瘤发生的细胞。
SV40 infection of human cells results in both transformation and lytic infection. We have used origin-defective viral mutants which are unable to replicate in permissive cells to help analysis of transformation. Expression of large T antigen (T ag) and small t antigen results in the altered growth phenotypes characteristic of transformation in other species. Human diploid fibroblasts (HF) have a limited lifespan and undergo senescence; T ag results in extension of lifespan but only in rare cases are the cells capable of continuous growth and are immortal. We have developed matched sets of non-immortal and immortal transformed HF for assessment of the steps required for immortalization. Results are summarized to characterize both T-dependent and T-independent functions. A novel growth suppressor gene SEN6 has been identified, the inactivation of which is required for immortalization; it may also serve as a marker to distinguish cells in which SV40 is replicating from those in which it is responsible for tumorigenesis.