RECOMBINANT RETROVIRUSES ENCODING SIMIAN-VIRUS 40 LARGE T-ANTIGEN AND POLYOMAVIRUS LARGE AND MIDDLE T-ANTIGENS

RECOMBINANT RETROVIRUSES ENCODING SIMIAN-VIRUS 40 LARGE T-ANTIGEN AND POLYOMAVIRUS LARGE AND MIDDLE T-ANTIGENS
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DOI:
10.1128/mcb.6.4.1204
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发表时间:
1986-04-01
影响因子:
5.3
通讯作者:
SHARP, PA
SHARP, PA
中科院分区:
生物学2区
文献类型:
--
作者:
JAT, PS;CEPKO, CL;SHARP, PA

文献摘要

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我们使用鼠逆转录病毒穿梭载体系统构建重组体,能够组成型表达猿猴病毒40(SV-409)大T抗原和多瘤病毒大和中T抗原以及对G418的抗性。随后,这些重组体用于产生产生携带每种病毒致癌基因的缺陷型无辅助病毒逆转录病毒的细胞系。用这些重组逆转录病毒分析病毒基因在大鼠F111细胞转化中的作用。多瘤病毒中T抗原单独表达导致高度致瘤性的细胞系,而多瘤病毒大T抗原表达导致形态学、非贴壁依赖性生长和致瘤性标准不变的细胞系。更令人惊讶的是,SV 40大T表达细胞系没有致瘤性,尽管它们含有升高水平的细胞p53并且在软琼脂中具有高的平板接种效率。这些结果表明,SV 40大T抗原不是像多瘤病毒中T抗原那样的急性转化基因,而是类似于myc和腺病毒EIa等建立基因。
We used a murine retrovirus shuttle vector system to construct recombinants capable of constitutively expressing the simian virus 40 (SV-409) large T antigen and the poylomavirus large and middle T antigens as well as resistance to G418. Subsequently, these recombinants were used to generate cell lines that produced defective helper-free retroviruses carrying each of the viral oncogenes. These recombinant retroviruses were used to analyze the role of the viral genes in transformation of rat F111 cells. Expression of the polyomavirus middle T antigen alone resulted in cell lines that were highly tumorigenic, whereas expression of the polyomavirus large T resulted in cell lines that were unaltered by the criteria of morphology, anchorage-independent growth, and tumorigenicity. More surprisingly, SV40 large T-expressing cell lines were not tumorigenic despite the fact that they contained elevated levels of cellular p53 and had a high plating efficiency in soft agar. These results suggest that the SV40 large T antigen is not an acute transforming gene like the polyomavirus middle T antigen but is similar to the establishment genes such as myc and adenovirus EIa.