Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: amplification of AKT1 in a primary human gastric adenocarcinoma.
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 molecularly 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.
D000230:Adenocarcinoma / Q000235:genetics*; D000818:Animals; D003001:Cloning, Molecular; D004273:DNA, Neoplasm / Q000235:genetics*; D004274:DNA, Recombinant; D004279:DNA, Viral / Q000235:genetics; D005784:Gene Amplification; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics*; D051379:Mice; D008806:Mice, Inbred AKR / Q000235:genetics / Q000382:microbiology; D008908:Mink Cell Focus-Inducing Viruses / Q000235:genetics* / Q000302:isolation & purification; D051058:Oncogene Protein v-akt; D009857:Oncogenes; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt; D011519:Proto-Oncogenes; D012191:Retroviridae Proteins / Q000235:genetics*; D015682:Retroviridae Proteins, Oncogenic; D012689:Sequence Homology, Nucleic Acid; D013274:Stomach Neoplasms / Q000235:genetics*; D013945:Thymoma / Q000235:genetics
D004273:DNA, Neoplasm; D004274:DNA, Recombinant; D004279:DNA, Viral; D011518:Proto-Oncogene Proteins; D012191:Retroviridae Proteins; D015682:Retroviridae Proteins, Oncogenic; C494918:AKT1 protein, human; C494921:AKT2 protein, human; C494922:Akt2 protein, mouse; D051058:Oncogene Protein v-akt; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt