MOLECULAR-CLONING OF THE AKT ONCOGENE AND ITS HUMAN HOMOLOGS AKT1 AND AKT2 - AMPLIFICATION OF AKT1 IN A PRIMARY HUMAN GASTRIC ADENOCARCINOMA
MOLECULAR-CLONING OF THE AKT ONCOGENE AND ITS HUMAN HOMOLOGS AKT1 AND AKT2 - AMPLIFICATION OF AKT1 IN A PRIMARY HUMAN GASTRIC ADENOCARCINOMA
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DOI：
10.1073/pnas.84.14.5034
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发表时间：
1987-07-01
影响因子：
11.1
通讯作者：
STAAL, SP
中科院分区：
文献类型：
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作者：
STAAL, SP
先前的一份报告描述了从AKR小鼠的自发性胸腺瘤中分离到一种直接转化的逆转录病毒AKT8。AKT8前病毒现在已经从一个转化的非产生细胞系中进行了分子克隆。病毒基因组包含病毒和非病毒的细胞相关序列；非病毒序列被命名为v-AKT，推测为AKT8病毒的致癌基因。该基因与测试的其他16个癌基因缺乏同源性。克隆的前病毒在体外细胞传代过程中经历了部分缺失，这阻碍了对该分子克隆转化能力的直接证明。克隆了v-AKT癌基因的两个人类同源物AKT1和AKT2。对225个涉及AKT1基因变化的人类肿瘤的调查发现，在所测试的五种胃腺癌中，其中一种的AKT1基因扩增了20倍。结果表明，AKT8具有直接转化逆转录病毒的特征结构，其基因来源于高度保守的细胞序列，可能与某些人类恶性肿瘤的发病机制有关。
A previous report described the isolation of a directly transforming retrovirus, AKT8, from a spontaneous thymoma of an AKR mouse. The AKT8 provirus has now been moleculary cloned from a transformed, nonproducer cell line. The virus genome contains both viral and nonviral, cell-related sequences; the nonviral sequence has been designated v-akt, the presumed viral oncogene of the AKT8 virus. This gene lacks homology to the 16 other oncogenes tested. The cloned provirus has undergone a partial deletion, during cell passage in vitro, that prevents direct demonstration of the transforming ability of this molecular clone. Two human homologues of the v-akt oncogene, AKT1 and AKT2, were cloned. A survey of 225 human tumors for changes involving AKT1 led to the discovery of a 20-fold amplification of this gene in one of the five gastric adenocarcinomas tested. The results demonstrate that AKT8 has the characteristic structure of a directly transforming retrovirus and that it contains a gene derived from highly conserved cellular sequences that may be involved in the pathogenesis of some human malignancies.