REVERSAL OF ONCOGENESIS BY THE EXPRESSION OF A MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I GENE
REVERSAL OF ONCOGENESIS BY THE EXPRESSION OF A MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I GENE
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DOI：
10.1126/science.3975631
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发表时间：
1985-01-01
期刊：
影响因子：
56.9
通讯作者：
JAY, G
中科院分区：
文献类型：
--
作者：
TANAKA, K;ISSELBACHER, KJ;JAY, G
经典的移植抗原(主要的组织相容性复合体I类抗原)在宿主对表达外源抗原的细胞的防御中起着关键作用。一些自然发生的肿瘤和病毒转化的细胞显示出对这些表面抗原的全面抑制。由于I类分子是将肿瘤细胞上的新抗原呈递给细胞毒性T淋巴细胞所必需的，它们的缺失可能会导致这些肿瘤逃脱免疫监视。为了测试这种可能性，将一个功能性的I类基因导入到人腺病毒12转化的小鼠细胞中，这些细胞不表达可检测到的I类抗原水平；对转化体进行了检测，以检测转基因基因的表达和致癌性的变化。通过DNA介导的基因转移将单一的I类基因导入高致瘤性的腺病毒12转化的细胞中，足以消除这些细胞的致瘤性。这一发现对于调节某些肿瘤的恶性表型，以及通过去抑制内源性第I类基因来调节致瘤性具有重要意义。
The classical transplantation antigens (the major histocompatibility complex class I antigens) play a key role in host defense against cells expressing foreign antigens. Several naturally occurring tumors and virally transformed cells show an overall suppression of these surface antigens. Since the class I molecules are required in the presentation of neoantigens on tumor cells to the cytotoxic T lymphocytes, their absence from the cell surface may lead to the escape of these tumors from immunosurveillance. To test this possibility, a functional class I gene was transfected into human adenovirus 12-transformed mouse cells that do not express detectable levels of class I antigens; the transformants were tested for expression of the transfected gene and for changes in oncogenicity. The expression of a single class I gene, introduced by DNA-mediated gene transfer into highly tumorigenic adenovirus 12-transformed cells, was sufficient to abrogate the oncogenicity of these cells. This finding has important implications for the regulation of the malignant phenotype in certain tumors and for the potential modulation of oncogenicity through derepression of the endogenous class I genes.