Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1985 Jul;55(1):23–33. doi: 10.1128/jvi.55.1.23-33.1985

Rapid induction of hemopoietic neoplasms in newborn mice by a raf(mil)/myc recombinant murine retrovirus.

U R Rapp, J L Cleveland, T N Fredrickson, K L Holmes, H C Morse 3rd, H W Jansen, T Patschinsky, K Bister
PMCID: PMC254893  PMID: 4009794

Abstract

3611 MSV, a raf oncogene-transducing murine retrovirus, induced fibrosarcomas in newborn mice after a latency of 4 to 8 weeks. In contrast, newly constructed recombinant murine retroviruses carrying the myc oncogene did not induce tumors before greater than or equal to 9 weeks. A combination of both oncogenes in an infectious murine retrovirus induced hematopoietic neoplasms in addition to less prominent fibrosarcomas and pancreatic acinar dysplasia 1 to 3 weeks after inoculation. The hematological neoplasms consisted of immunoblastic lymphomas of T- and B-lineage cells and erythroblastosis. Cell lines from these tumors could be readily established in culture in regular medium, whereas culture of cells from raf oncogene-induced tumors required the addition of interleukin 3. In parallel to the synergistic action of both oncogenes on hematopoietic cells in vivo, we found that raf oncogene-induced transformation of fibroblast cell lines in culture was enhanced by the addition of myc, which by itself did not morphologically transform these permanent cell lines. We conclude that concomitant expression of raf and myc oncogenes in hematopoietic cells and fibroblastic cell lines enhances their respective transforming activities.

Full text

PDF
23

Images in this article

26Image
on p.26
28Image
on p.28
30Image
on p.30
31Image
on p.31

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alexander R. W., Moscovici C., Vogt P. K. Avian oncovirus Mill Hill No. 2: pathogenicity in chickens. J Natl Cancer Inst. 1979 Feb;62(2):359–366. [PubMed] [Google Scholar]
  2. Alitalo K., Bishop J. M., Smith D. H., Chen E. Y., Colby W. W., Levinson A. D. Nucleotide sequence to the v-myc oncogene of avian retrovirus MC29. Proc Natl Acad Sci U S A. 1983 Jan;80(1):100–104. doi: 10.1073/pnas.80.1.100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Armelin H. A., Armelin M. C., Kelly K., Stewart T., Leder P., Cochran B. H., Stiles C. D. Functional role for c-myc in mitogenic response to platelet-derived growth factor. Nature. 1984 Aug 23;310(5979):655–660. doi: 10.1038/310655a0. [DOI] [PubMed] [Google Scholar]
  4. Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bishop J. M. Cellular oncogenes and retroviruses. Annu Rev Biochem. 1983;52:301–354. doi: 10.1146/annurev.bi.52.070183.001505. [DOI] [PubMed] [Google Scholar]
  6. Bunte T., Donner P., Pfaff E., Reis B., Greiser-Wilke I., Schaller H., Moelling K. Inhibition of DNA binding of purified p55v-myc in vitro by antibodies against bacterially expressed myc protein and a synthetic peptide. EMBO J. 1984 Aug;3(8):1919–1924. doi: 10.1002/j.1460-2075.1984.tb02068.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. CARR J. G. Kidney carcinomas of the fowl induced by the MH2 reticuloendothelioma virus. Br J Cancer. 1960 Mar;14:77–82. doi: 10.1038/bjc.1960.9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Coll J., Righi M., Taisne C., Dissous C., Gegonne A., Stehelin D. Molecular cloning of the avian acute transforming retrovirus MH2 reveals a novel cell-derived sequence (v-mil) in addition to the myc oncogene. EMBO J. 1983;2(12):2189–2194. doi: 10.1002/j.1460-2075.1983.tb01722.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cooper J. A., Hunter T. Identification and characterization of cellular targets for tyrosine protein kinases. J Biol Chem. 1983 Jan 25;258(2):1108–1115. [PubMed] [Google Scholar]
  10. Davidson W. F., Fredrickson T. N., Rudikoff E. K., Coffman R. L., Hartley J. W., Morse H. C., 3rd A unique series of lymphomas related to the Ly-1+ lineage of B lymphocyte differentiation. J Immunol. 1984 Aug;133(2):744–753. [PubMed] [Google Scholar]
  11. Der C. J., Krontiris T. G., Cooper G. M. Transforming genes of human bladder and lung carcinoma cell lines are homologous to the ras genes of Harvey and Kirsten sarcoma viruses. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3637–3640. doi: 10.1073/pnas.79.11.3637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Downward J., Yarden Y., Mayes E., Scrace G., Totty N., Stockwell P., Ullrich A., Schlessinger J., Waterfield M. D. Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature. 1984 Feb 9;307(5951):521–527. doi: 10.1038/307521a0. [DOI] [PubMed] [Google Scholar]
  13. Duesberg P. H. Retroviral transforming genes in normal cells? Nature. 1983 Jul 21;304(5923):219–226. doi: 10.1038/304219a0. [DOI] [PubMed] [Google Scholar]
  14. Fredrickson T. N., Langdon W. Y., Hoffman P. M., Hartley J. W., Morse H. C., 3rd Histologic and cell surface antigen studies of hematopoietic tumors induced by Cas-Br-M murine leukemia virus. J Natl Cancer Inst. 1984 Feb;72(2):447–454. [PubMed] [Google Scholar]
  15. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  16. Greenberg M. E., Ziff E. B. Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature. 1984 Oct 4;311(5985):433–438. doi: 10.1038/311433a0. [DOI] [PubMed] [Google Scholar]
  17. Hwang L. S., Park J., Gilboa E. Role of intron-contained sequences in formation of moloney murine leukemia virus env mRNA. Mol Cell Biol. 1984 Nov;4(11):2289–2297. doi: 10.1128/mcb.4.11.2289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jansen H. W., Lurz R., Bister K., Bonner T. I., Mark G. E., Rapp U. R. Homologous cell-derived oncogenes in avian carcinoma virus MH2 and murine sarcoma virus 3611. Nature. 1984 Jan 19;307(5948):281–284. doi: 10.1038/307281a0. [DOI] [PubMed] [Google Scholar]
  19. Jansen H. W., Patschinsky T., Bister K. Avian oncovirus MH2: molecular cloning of proviral DNA and structural analysis of viral RNA and protein. J Virol. 1983 Oct;48(1):61–73. doi: 10.1128/jvi.48.1.61-73.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jansen H. W., Rückert B., Lurz R., Bister K. Two unrelated cell-derived sequences in the genome of avian leukemia and carcinoma inducing retrovirus MH2. EMBO J. 1983;2(11):1969–1975. doi: 10.1002/j.1460-2075.1983.tb01686.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kan N. C., Flordellis C. S., Garon C. F., Duesberg P. H., Papas T. S. Avian carcinoma virus MH2 contains a transformation-specific sequence, mht, and shares the myc sequence with MC29, CMII, and OK10 viruses. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6566–6570. doi: 10.1073/pnas.80.21.6566. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kelly K., Cochran B. H., Stiles C. D., Leder P. Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell. 1983 Dec;35(3 Pt 2):603–610. doi: 10.1016/0092-8674(83)90092-2. [DOI] [PubMed] [Google Scholar]
  23. Land H., Parada L. F., Weinberg R. A. Cellular oncogenes and multistep carcinogenesis. Science. 1983 Nov 18;222(4625):771–778. doi: 10.1126/science.6356358. [DOI] [PubMed] [Google Scholar]
  24. Land H., Parada L. F., Weinberg R. A. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 1983 Aug 18;304(5927):596–602. doi: 10.1038/304596a0. [DOI] [PubMed] [Google Scholar]
  25. Lautenberger J. A., Schulz R. A., Garon C. F., Tsichlis P. N., Papas T. S. Molecular cloning of avian myelocytomatosis virus (MC29) transforming sequences. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1518–1522. doi: 10.1073/pnas.78.3.1518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Little C. D., Nau M. M., Carney D. N., Gazdar A. F., Minna J. D. Amplification and expression of the c-myc oncogene in human lung cancer cell lines. Nature. 1983 Nov 10;306(5939):194–196. doi: 10.1038/306194a0. [DOI] [PubMed] [Google Scholar]
  27. Mark G. E., Rapp U. R. Primary structure of v-raf: relatedness to the src family of oncogenes. Science. 1984 Apr 20;224(4646):285–289. doi: 10.1126/science.6324342. [DOI] [PubMed] [Google Scholar]
  28. Marquardt H., Hunkapiller M. W., Hood L. E., Twardzik D. R., De Larco J. E., Stephenson J. R., Todaro G. J. Transforming growth factors produced by retrovirus-transformed rodent fibroblasts and human melanoma cells: amino acid sequence homology with epidermal growth factor. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4684–4688. doi: 10.1073/pnas.80.15.4684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Morse H. C., 3rd, Chused T. M., Boehm-Truitt M., Mathieson B. J., Sharrow S. O., Hartley J. W. XenCSA: cell surface antigens related to the major glycoproteins (gp70) of xenotropic murine leukemia viruses. J Immunol. 1979 Feb;122(2):443–454. [PubMed] [Google Scholar]
  30. Paterson M. C. Heritable cancer-prone disorders featuring carcinogen hypersensitivity and DNA repair deficiency. IARC Sci Publ. 1982;(39):57–86. [PubMed] [Google Scholar]
  31. Patschinsky T., Walter G., Bister K. Immunological analysis of v-myc gene products using antibodies against a myc-specific synthetic peptide. Virology. 1984 Jul 30;136(2):348–358. doi: 10.1016/0042-6822(84)90171-5. [DOI] [PubMed] [Google Scholar]
  32. Rapp U. R., Goldsborough M. D., Mark G. E., Bonner T. I., Groffen J., Reynolds F. H., Jr, Stephenson J. R. Structure and biological activity of v-raf, a unique oncogene transduced by a retrovirus. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4218–4222. doi: 10.1073/pnas.80.14.4218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Rapp U. R., Reynolds F. H., Jr, Stephenson J. R. New mammalian transforming retrovirus: demonstration of a polyprotein gene product. J Virol. 1983 Mar;45(3):914–924. doi: 10.1128/jvi.45.3.914-924.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Reddy E. P., Reynolds R. K., Santos E., Barbacid M. A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene. Nature. 1982 Nov 11;300(5888):149–152. doi: 10.1038/300149a0. [DOI] [PubMed] [Google Scholar]
  35. Reddy E. P., Reynolds R. K., Watson D. K., Schultz R. A., Lautenberger J., Papas T. S. Nucleotide sequence analysis of the proviral genome of avian myelocytomatosis virus (MC29). Proc Natl Acad Sci U S A. 1983 May;80(9):2500–2504. doi: 10.1073/pnas.80.9.2500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Rio D., Robbins A., Myers R., Tjian R. Regulation of simian virus 40 early transcription in vitro by a purified tumor antigen. Proc Natl Acad Sci U S A. 1980 Oct;77(10):5706–5710. doi: 10.1073/pnas.77.10.5706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Silver J. E., Fredrickson T. N. A new gene that controls the type of leukemia induced by Friend murine leukemia virus. J Exp Med. 1983 Aug 1;158(2):493–505. doi: 10.1084/jem.158.2.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Stiles C. D., Capone G. T., Scher C. D., Antoniades H. N., Van Wyk J. J., Pledger W. J. Dual control of cell growth by somatomedins and platelet-derived growth factor. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1279–1283. doi: 10.1073/pnas.76.3.1279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Sutrave P., Bonner T. I., Rapp U. R., Jansen H. W., Patschinsky T., Bister K. Nucleotide sequence of avian retroviral oncogene v-mil: homologue of murine retroviral oncogene v-raf. Nature. 1984 May 3;309(5963):85–88. doi: 10.1038/309085a0. [DOI] [PubMed] [Google Scholar]
  40. Tabin C. J., Bradley S. M., Bargmann C. I., Weinberg R. A., Papageorge A. G., Scolnick E. M., Dhar R., Lowy D. R., Chang E. H. Mechanism of activation of a human oncogene. Nature. 1982 Nov 11;300(5888):143–149. doi: 10.1038/300143a0. [DOI] [PubMed] [Google Scholar]
  41. Taparowsky E., Suard Y., Fasano O., Shimizu K., Goldfarb M., Wigler M. Activation of the T24 bladder carcinoma transforming gene is linked to a single amino acid change. Nature. 1982 Dec 23;300(5894):762–765. doi: 10.1038/300762a0. [DOI] [PubMed] [Google Scholar]
  42. Taub R., Kirsch I., Morton C., Lenoir G., Swan D., Tronick S., Aaronson S., Leder P. Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7837–7841. doi: 10.1073/pnas.79.24.7837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Temin H. M. Do we understand the genetic mechanisms of oncogenesis? Keynote address for Honey Harbor meeting on cellular and molecular biology of neoplasia, October 2-6, 1983. J Cell Physiol Suppl. 1984;3:1–11. doi: 10.1002/jcp.1041210403. [DOI] [PubMed] [Google Scholar]
  44. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Twardzik D. R., Todaro G. J., Marquardt H., Reynolds F. H., Jr, Stephenson J. R. Transformation induced by Abelson murine leukemia virus involves production of a polypeptide growth factor. Science. 1982 May 21;216(4548):894–897. doi: 10.1126/science.6177040. [DOI] [PubMed] [Google Scholar]
  46. Walther N., Lurz R., Patschinsky T., Jansen H. W., Bister K. Molecular cloning of proviral DNA and structural analysis of the transduced myc oncogene of avian oncovirus CMII. J Virol. 1985 May;54(2):576–585. doi: 10.1128/jvi.54.2.576-585.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. de Larco J. E., Todaro G. J. Growth factors from murine sarcoma virus-transformed cells. Proc Natl Acad Sci U S A. 1978 Aug;75(8):4001–4005. doi: 10.1073/pnas.75.8.4001. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES