Abstract
The directly transforming murine retrovirus, AKT8, was isolated from a spontaneous AKR thymoma and carries the cell-derived viral oncogene, akt. We have now shown that this virus produces thymic lymphomas after inoculation of susceptible mouse strains. The presence of the AKT8 genome in the DNA of the virus-induced tumors was demonstrated by Southern blotting using an akt-specific probe. These results establish the in vivo pathogenicity of the AKT8 virus and its akt oncogene, and imply a potential role for the cellular akt proto-oncogene in tumor development.
Full Text
The Full Text of this article is available as a PDF (372.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Chattopadhyay S. K., Cloyd M. W., Linemeyer D. L., Lander M. R., Rands E., Lowy D. R. Cellular origin and role of mink cell focus-forming viruses in murine thymic lymphomas. Nature. 1982 Jan 7;295(5844):25–31. doi: 10.1038/295025a0. [DOI] [PubMed] [Google Scholar]
- Cloyd M. W. Characterization of target cells for MCF viruses in AKR mice. Cell. 1983 Jan;32(1):217–225. doi: 10.1016/0092-8674(83)90512-3. [DOI] [PubMed] [Google Scholar]
- Cloyd M. W., Hartley J. W., Rowe W. P. Genetic study of lymphoma induction by AKR mink cell focus-inducing virus in AKR x NFS crosses. J Exp Med. 1981 Aug 1;154(2):450–457. doi: 10.1084/jem.154.2.450. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cloyd M. W., Hartley J. W., Rowe W. P. Lymphomagenicity of recombinant mink cell focus-inducing murine leukemia viruses. J Exp Med. 1980 Mar 1;151(3):542–552. doi: 10.1084/jem.151.3.542. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Corcoran L. M., Adams J. M., Dunn A. R., Cory S. Murine T lymphomas in which the cellular myc oncogene has been activated by retroviral insertion. Cell. 1984 May;37(1):113–122. doi: 10.1016/0092-8674(84)90306-4. [DOI] [PubMed] [Google Scholar]
- Elder J. H., Gautsch J. W., Jensen F. C., Lerner R. A., Hartley J. W., Rowe W. P. Biochemical evidence that MCF murine leukemia viruses are envelope (env) gene recombinants. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4676–4680. doi: 10.1073/pnas.74.10.4676. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fredrickson T. N., Morse H. C., 3rd, Rowe W. P. Spontaneous tumors of NFS mice congenic for ecotropic murine leukemia virus induction loci. J Natl Cancer Inst. 1984 Aug;73(2):521–524. doi: 10.1093/jnci/73.2.521. [DOI] [PubMed] [Google Scholar]
- Hartley J. W., Rowe W. P. Clonal cells lines from a feral mouse embryo which lack host-range restrictions for murine leukemia viruses. Virology. 1975 May;65(1):128–134. doi: 10.1016/0042-6822(75)90013-6. [DOI] [PubMed] [Google Scholar]
- Hartley J. W., Rowe W. P. Naturally occurring murine leukemia viruses in wild mice: characterization of a new "amphotropic" class. J Virol. 1976 Jul;19(1):19–25. doi: 10.1128/jvi.19.1.19-25.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hartley J. W., Wolford N. K., Old L. J., Rowe W. P. A new class of murine leukemia virus associated with development of spontaneous lymphomas. Proc Natl Acad Sci U S A. 1977 Feb;74(2):789–792. doi: 10.1073/pnas.74.2.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kozak C. A., Rowe W. P. Genetic mapping of ecotropic murine leukemia virus-inducing loci in six inbred strains. J Exp Med. 1982 Feb 1;155(2):524–534. doi: 10.1084/jem.155.2.524. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LYNCH C. J. The R.I.L. strain of mice: its relation to the leukemic AK strain and AKR substrains. J Natl Cancer Inst. 1954 Aug;15(1):161–176. [PubMed] [Google Scholar]
- Li Y., Holland C. A., Hartley J. W., Hopkins N. Viral integration near c-myc in 10-20% of mcf 247-induced AKR lymphomas. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6808–6811. doi: 10.1073/pnas.81.21.6808. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Donnell P. V., Fleissner E., Lonial H., Koehne C. F., Reicin A. Early clonality and high-frequency proviral integration into the c-myc locus in AKR leukemias. J Virol. 1985 Aug;55(2):500–503. doi: 10.1128/jvi.55.2.500-503.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rasheed S., Gardner M. B., Chan E. Amphotropic host range of naturally occuring wild mouse leukemia viruses. J Virol. 1976 Jul;19(1):13–18. doi: 10.1128/jvi.19.1.13-18.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rowe W. P. Leukemia virus genomes in the chromosomal DNA of the mouse. Harvey Lect. 1978;71:173–192. [PubMed] [Google Scholar]
- Rowe W. P., Pincus T. Quantitative studies of naturally occurring murine leukemia virus infection of AKR mice. J Exp Med. 1972 Feb 1;135(2):429–436. doi: 10.1084/jem.135.2.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Selten G., Cuypers H. T., Berns A. Proviral activation of the putative oncogene Pim-1 in MuLV induced T-cell lymphomas. EMBO J. 1985 Jul;4(7):1793–1798. doi: 10.1002/j.1460-2075.1985.tb03852.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Selten G., Cuypers H. T., Zijlstra M., Melief C., Berns A. Involvement of c-myc in MuLV-induced T cell lymphomas in mice: frequency and mechanisms of activation. EMBO J. 1984 Dec 20;3(13):3215–3222. doi: 10.1002/j.1460-2075.1984.tb02281.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Staal S. P., Hartley J. W., Rowe W. P. Isolation of transforming murine leukemia viruses from mice with a high incidence of spontaneous lymphoma. Proc Natl Acad Sci U S A. 1977 Jul;74(7):3065–3067. doi: 10.1073/pnas.74.7.3065. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Staal S. P. Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: amplification of AKT1 in a primary human gastric adenocarcinoma. Proc Natl Acad Sci U S A. 1987 Jul;84(14):5034–5037. doi: 10.1073/pnas.84.14.5034. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Steffen D. Proviruses are adjacent to c-myc in some murine leukemia virus-induced lymphomas. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2097–2101. doi: 10.1073/pnas.81.7.2097. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsichlis P. N. Oncogenesis by Moloney murine leukemia virus. Anticancer Res. 1987 Mar-Apr;7(2):171–180. [PubMed] [Google Scholar]
- Vijaya S., Steffen D. L., Kozak C., Robinson H. L. Dsi-1, a region with frequent proviral insertions in Moloney murine leukemia virus-induced rat thymomas. J Virol. 1987 Apr;61(4):1164–1170. doi: 10.1128/jvi.61.4.1164-1170.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Villeneuve L., Rassart E., Jolicoeur P., Graham M., Adams J. M. Proviral integration site Mis-1 in rat thymomas corresponds to the pvt-1 translocation breakpoint in murine plasmacytomas. Mol Cell Biol. 1986 May;6(5):1834–1837. doi: 10.1128/mcb.6.5.1834. [DOI] [PMC free article] [PubMed] [Google Scholar]