Induction of Hematopoietic Tumors Using a Viral Construct Containing c-myc cDNA from Normal Mouse Spleen

  • Linda Wolff
  • J. Frederic Mushinski
  • Eli Gilboa
  • Herbert C. MorseIII
Conference paper
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 132)


Deregulated expression of the c-myc protooncogene is assumed to be a major contributing factor to the development of plasmacytomas in pristane-primed BALB/c mice (reviewed in Potter, 1986) and murine T cell lymphomas induced by AKR and Moloney murine leukemia viruses (MuLV) (Steffen 1984, Selden et al. 1984, Li et al. 1 984, Corcoran et al. 1984). Studies on the c-myc expression in plasmacytomas suggest that myc can be deregulated by a variety of mechanisms. These include stabilization of the myc message due to an altered transcriptional unit (Piechaczyk et a1. 1985), removal of cis-acting regulatory sequences (Yang et al. 1985) and augmentation of transcriptional activity resulting from apposed IgH enhancer sequences (Corcoran, 1985). These studies provide substantial inferential support for the view that aberrant expression of myc is central to the trarisformation of murine plasma cells and T cells but direct evidence to buttress this argument has been lacking. Efforts to develop this evidence have taken several complementary directions, all resulting in abnormally high levels of myc expression in somatic cells. These include the development of transgenic mice with murine or human c-myc genes driven by selected promoter/enhancer sequences (Stewart et al. 1 984; Adams et al. 1986) or infection of mice with recombinant murine retroviruses containing avian v-myc genes (Morse et al. 1986; Potter et al. 1986). The avian v-myc genes are known to contain numerous coding region mutations in comparison to normal avian c-myc sequences and also differ from normal murine c-myc genes (Papas and Lautenberger 1985). Since sequence differences among avian v-myc genes appear to contribute to variations in their oncogenic potentials (Enrietto et al. 1984), we wished to determine if overexpression of a normal murine c-myc gene in mice would result in the development of tumors. This report describes the features of two new recombinant murine retroviruses containing normal mouse c-myc coding sequences and the results obtained when pseudotypes of these viruses were used to infect adult, pristane-primed BALB/c mice.


Helper Virus Specific Cell Surface Antigen Pristane Treatment Confer G418 Resistance Spontaneous Mammary Adenocarcinoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adams JM, Gerondakis S, Webb E, Corcoran LM, Cory S (1983) Cellular myc oncogene is altered by chromosomal translocation to an immunoglobulin locus in murine plasmacytomas and is rearranged similarly in human Burkitt’s lymphomas. Proc Natl Acad Sci USA 80: 1982–1986PubMedCrossRefGoogle Scholar
  2. Adams JM, Harris AW, Pinkert CA, Corcoran LM, Alexander WS, Cory S, Palmiter RD, Brinster RL (1985) The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature 318: 533–538PubMedCrossRefGoogle Scholar
  3. Baumbach WR, Stanley ER, Cole MD (1986) Induction of clonal monocyte macrophage tumors in vivo by a mouse c-myc retrovirus: evidence for secondary transforming events. Current Topics in Microbiology and Immunology (this volume)Google Scholar
  4. Beck E, Ludwig G, Auerswald EA, Reiss B, Schaller H (1982) Nucleotide sequence and exact location of the neomycin phosphotransferase gene from transposon Tn5. Gene 19: 327–336PubMedCrossRefGoogle Scholar
  5. Corcoran LM, Adams JM, Dunn AR, Cory S (1984) Murine T lymphomas in which the cellular myc oncogene has been activated by retroviral insertion. Cell 37: 113–122PubMedCrossRefGoogle Scholar
  6. Corcoran LM, Cory S, Adams JM (1985) Transposition of the immunoglobulin heavy chain enhancer to the myc oncogene in a murine plasmacytoma. Cell 40: 71–79PubMedCrossRefGoogle Scholar
  7. Davidson WF, Frederickson TN, Rudikoff EK, Coffman RL, Hartley JW, Morse HC, III (1984) A unique series of lymphomas related to the Ly-1+ lineage of B lymphocyte differentiation. J Immunol 133: 744–753PubMedGoogle Scholar
  8. Enrietto PJ, Payne LN, Hayman MJ (1 983) Recovered avian myelocytomatosis virus that induces lymphomas in chickens: pathogenic properties and their molecular basis. Cell 35: 369–379Google Scholar
  9. Gilboa E, Park J, Kolbe M, Hwang S, Kucherlapati R, Noonan K, Freeman H (1982) Transduction and expression of nonselectable genes using retrovirus-derived vectors. In: Gluzman Y (ed) Eukaryotic viral vectors. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, p 145–l5lGoogle Scholar
  10. Holmes KL, Pierce JH, Davidson WS, Morse HC, III (1986) Murine hematopoietic cells with Pre B or Pre B/myeloid characteristics are generated by in vitro transformation with retroviruses containing Fes, Ras, Abl and Src oncogenes. J Exp Med (in press)Google Scholar
  11. Li Y, Holland CA, Hartley JW, Hopkins N (1984) Viral integration near c-myc in 10–20% of MCF 247-induced AKR lymphomas. Proc Natl Acad Sci USA 81: 6808–6811PubMedCrossRefGoogle Scholar
  12. Morse HC, III, Hartley JW, Frederickson TN, Yetter RA, Cleveland JL, Majumdar C, Rapp UR (1986) Tumors of newborn NFS/N mice infected with murine retroviruses containing avian v-myc. Current Topics in Microbiology and Immunology (this volume)Google Scholar
  13. Osserman EF, Lawlor DF (1966) Serums and urinary lysozyme (muramidase) in monocytic and monomyelocytic leukemia. J Exp Med 124: 921–952PubMedCrossRefGoogle Scholar
  14. Papas TS, Lautenberger JA (1985) Sequence curiosity in v-myc oncogene. Nature 318: 237PubMedCrossRefGoogle Scholar
  15. Piechaczyk M, Yang J-Q, Banchard J-M, Jeanteur P, Marcu KB (1985) Post-transcriptional mechanisms are responsible for accumulation of truncated c-myc RNAs in murine plasma cell tumors. Cell 42: 589–597PubMedCrossRefGoogle Scholar
  16. Potter M (1986) Progression in plasmacytoma development. Adv in Viral Onc, Vol 6 (in press)Google Scholar
  17. Potter M, Wax J, Mushinski E, Brust S, Babonits M, Wiener F, Mushinski JF, Mezebish D, Skurla R, Rapp U, Morse HC, III (1986) Rapid induction of plasmacytomas in mice by pristane and a murine recombinant retrovirus containing an avian v-myc and a defective raf raf oncogene. Current Topics in Microbiology and Immunology (this volume)Google Scholar
  18. Selten G, Cuypers HT, Zijlstra M, Melief C, Berns A (1984) Involvement of c-myc in MuLV-induced T cell lymphomas in mice: frequency and mechanisms of activation. EMBO J 3: 3215–3222PubMedGoogle Scholar
  19. Stanton LW, Watt R, Marcu KB (1983) Translocation, breakage and truncated transcripts of c-myc oncogene in murine plasmacytomas. Nature 303: 401–406PubMedCrossRefGoogle Scholar
  20. Steffen D (1984) Proviruses are adjacent to c-myc in some murine leukemia virus induced lymphomas. Proc Natl Acad Sci USA 81: 2097–2101PubMedCrossRefGoogle Scholar
  21. Stewart TA, Pattengale PK, Leder P (1984) Spontaneous mammary adenocarcinomas in transgenic mice that carry and express MTV/myc fusion genes. Cell 38: 627–637PubMedCrossRefGoogle Scholar
  22. Yam LT, Li CY, Crosby WH (1971) Cytochemical identification of monocytes and granulocytes. Am J Clin Pathol 55: 283–297PubMedGoogle Scholar
  23. Yang J-Q, Bauer SR, Mushinski JF, Marcu KB (1985) Chromosomal translocations clustered 5’ of the murine c-myc gene qualitatively affect promotor usage: implications for the site of normal c-myc regulation. EMBO J 4: 1441–1447PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1986

Authors and Affiliations

  • Linda Wolff
    • 1
  • J. Frederic Mushinski
    • 1
  • Eli Gilboa
    • 2
  • Herbert C. MorseIII
    • 3
  1. 1.Laboratory of GeneticsNational Cancer Institute, National Institutes of HealthBethesdaUSA
  2. 2.Department of Molecular BiologyPrinceton UniversityPrincetonUSA
  3. 3.Laboratory of ImmunopathologyNational Institute of Allergy and Infectious Diseases, National Institutes of HealthBethesdaUSA

Personalised recommendations