ROLE OF ADENOVIRUS TYPE-5 AND TYPE-12 EARLY REGION-1B TUMOR-ANTIGENS IN ONCOGENIC TRANSFORMATION

ROLE OF ADENOVIRUS TYPE-5 AND TYPE-12 EARLY REGION-1B TUMOR-ANTIGENS IN ONCOGENIC TRANSFORMATION
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DOI:
10.1016/0042-6822(83)90369-0
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发表时间:
1983-01-01
期刊:
影响因子:
3.7
通讯作者:
VANDEREB, AJ
VANDEREB, AJ
中科院分区:
医学3区
文献类型:
--
作者:
BERNARDS, R;SCHRIER, PI;VANDEREB, AJ

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无胸腺裸鼠中腺病毒5型(Ad 5)转化的细胞和Ad 12转化的细胞之间的致癌潜力的差异由早期区域Ib指定。为了确定2种早期区域1b(E1 b)肿瘤抗原中的哪一种负责观察到的致瘤性差异,构建了2种Ad 5/Ad 12杂交质粒:一种允许表达Ad 5 19 kD [千道尔顿]和Ad 12 54 kD E1 b蛋白,另一种允许表达Ad 5 58 kD和Ad 12 19 kD E1 b多肽。两种杂交质粒均含有两种血清型的完整E1 a区域。嵌合质粒用于转化幼鼠肾细胞的原代培养物,并在无胸腺裸鼠中测试所得转化细胞的致瘤性。发现致瘤性的程度由大E1 b肿瘤抗原的特性决定。用Ad 12区E1质粒转化的细胞进行的研究表明,该蛋白的表达仍然是转化细胞的致癌表型表现所必需的,在该质粒中编码19 kD肿瘤抗原的基因发生突变。
The difference in oncogenic potential between adenovirus type 5 (Ad5)- and Ad12-transformed cells in athymic nude mice is specified by early region lb. In order to determine which of the 2 early region 1b (E1b) tumor antigens is responsible for the observed difference in oncogenicity, 2 Ad5/Ad12 hybrid plasmids were constructed: one allowing expression of the Ad5 19kD [kilodalton] and Ad12 54kD E1b proteins, the other of the Ad5 58kD plus Ad12 19kD E1b polypeptides. Both hybrid plasmids contain the intact E1a regions of both serotypes. The chimeric plasmids were used to transform primary cultures of baby rat kidney cells and the resulting transformed cells were tested for oncogenicity in athymic nude mice. It was found that the degree of oncogenicity is determined by the identity of the large E1b tumor antigen. Studies with cells transformed by an Ad12 region E1 plasmid in which the gene coding for the 19kD tumor antigen was mutated showed that expression of this protein is nevertheless required for manifestations of the oncogenic phenotype of the transformed cell.