Complex Regulation of c-myc Gene Expression in a Murine B Cell Lymphoma

  • R. A. Levine
  • J. E. McCormack
  • A. Buckler
  • G. E. Sonenshein
Conference paper
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 132)


Alterations in the structure of the c-myc gene have implicated this oncogene in many types of B cell neoplasias. Changes include chromosomal translocation to an immunoglobulin gene locus, retroviral insertion into the c-myc promoter, and gene amplification. While in most cases the change in c-myc gene structure leaves the protein product unaffected, the regulation of expression of the gene may be altered. In many cell systems, e.g. splenic lymphocytes, untransformed fibroblast lines, and rat liver (Kelly et. al., 1983, Campisi et al., 1984, Goyette et. al., 1984), expression of c-myc mRNA is low in quiescence and increases rapidly upon exit from the GO state. Quiescent B lymphocytes contain barely detectable levels of c-myc mRNA. Upon stimulation with the mitogen LPS, c-myc mRNA levels increase 20 to 30 fold within 2–3 hours (Kelly et al., 1983). Terminal differentiation is accompanied by a decrease in expression of c-myc mRNA (Campisi et al., 1984, Grosso and Pitot 1985, Lachman and Skoultchi, 1984). These results suggest a role for the c-myc gene in the control of proliferation and differentiation. Since maturation of B cells involves several stages of differentiation, including terminal differentiation to nonproliferating plasma cells, it seemed likely that alterations in c-myc gene regulation might lead to aberrant B cell growth and differentiation.


Daudi Cell Aberrant Transcript Cytoplasmic mRNA Message Stability Sense Strand Transcription 
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  1. Adams, J, Gerondakis, S, Webb, E, Mitchell, J, Bernard, O and Cory, S (1982) Transcriptionally active DNA region that rearranges frequently in murine lymphoid tumors. Proc Natl Acad Sci USA 79: 6996–6970Google Scholar
  2. Blanchard, JM, Piechaczyk, M, Dani, Ch, Chambard, JC, Franchi, A, Pouyssegur, J, and Jeanteur, Ph (1985) c-myc gene is transcribed at high rate in GQ-arrested fibroblasts and is post-transcriptionally regulated in response to growth factors. Nature 317: 443–445Google Scholar
  3. Boyd, A and Schrader, JW (1981) The regulation of growth and differentiation of a murine B-cell lymphoma: II. The inhibition of WEHI 231 by anti-immunoglobulin antibodies. J Immunol 126: 2466–2469PubMedGoogle Scholar
  4. Campisi, J, Gray, H, Pardee, AB, Dean, M, Sonenshein, GE (1984) Cell-cycle control of c-myc but not c-ras expression is lost following chemical transformation. Cell 36: 241–247.PubMedCrossRefGoogle Scholar
  5. Dani, Ch, Blancard, J M, Piechaczyk, M, El Sabouty, S, Marty, L, Jeanteur, Ph (1984) Extreme instability of myc mRNA in normal and transformed human cells. Proc Natl Acad Sci USA 81: 7046–7050PubMedCrossRefGoogle Scholar
  6. Dani, Ch, Mechti, N, Piechaczyk, M, Lebleu, Br Jeanteurr Ph, Blancard, JM (1985) Increased rate of degradation of c-myc mRNA in interferon-treated Daudi cells. Proc Natl Acad Sci USA 82: 4896–4899Google Scholar
  7. Dean, M, Kent, RB, Sonenshein, GE (1983) Transcriptional activation of immunoglobulin a heavy-chain genes by translocation of the c-myc oncogene. Nature (London) 305: 443–446CrossRefGoogle Scholar
  8. Dean, M, Levine, RA, and Campisi, J (1986) c-myc regulation during retinoic acid-induced differentiation of F9 cells is post-transcriptional and associated with growth arrest. Molec Cell Biol 6: 518–524Google Scholar
  9. Dony, L, Kessel, M, and Gruss, P (1985) Post-transcriptional control of myc and p53 expression during differentiation of the embryonal carcinoma cell line F9. Nature 317: 636–639PubMedCrossRefGoogle Scholar
  10. Goyette, M, Petropoulos, C, Shank, P, Fausto, N (1984) Regulated transcription of c-Ki-ras and c-myc during compensatory growth of rat liver. Mol Cell Biol 4: 1493–1498PubMedGoogle Scholar
  11. Greenberg, ME and Ziff, EB (1984) Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature 311: 433–438PubMedCrossRefGoogle Scholar
  12. Grosso, LE and Pitot, HC (1985) Transcriptional regulation of c-myc during chemically induced differentiation, Cancer Res 45: 847–850PubMedGoogle Scholar
  13. Kelly, K, Cochran, B, Stiles, C, Leder, P (1983) Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell 35: 603–610PubMedCrossRefGoogle Scholar
  14. McCormack, JE, Pepe, VH, Kent, RB, Dean, M, Marshak-Rothstein, A, Sonenshein, GE (1984) Specific regulation of c-myc oncogene expression in a murine B-cell lymphoma. Proc Natl Acad Sci USA 81: 5546–5550PubMedCrossRefGoogle Scholar
  15. Nishizuka, Y (1984) The role of protein kinase C in cell surface signal transduction and tumor promotion. Nature 308: 693–698PubMedCrossRefGoogle Scholar
  16. Piechaczyk, M, Yang, J-Q, Blanchard, JM, Jeanteur, Ph, Marcu, KB (1985) Posttranscriptional mechanisms are responsible for accumulation of truncated c-myc RNAs in murine plasma cell tumors. Cell 42: 589–597PubMedCrossRefGoogle Scholar
  17. Ponte P, Siekevitz, M, Schwartz, R, Gefter, M, and Sonenshein, GE (1981) Transcription of immunoglobulin heavy-chain sequences from the excluded allele. Nature 291: 594–596PubMedCrossRefGoogle Scholar
  18. Shen-Ong, G, Keath, E, Piccoli, S and Cole, M (1982) Novel myc oncogene RNA from abortive immunoglobulin-gene recombination in mouse plasmacytomas. Cell 31: 443–452PubMedCrossRefGoogle 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. Taub, R, Kirsch, I, Morton, C, Lenoir, G, Swan, D, Tronick, S, Aaronson, S, and Leder, P (1982) Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells. Proc Natl Acad Sci USA 79: 7837–7841PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1986

Authors and Affiliations

  • R. A. Levine
    • 1
  • J. E. McCormack
    • 1
  • A. Buckler
    • 1
  • G. E. Sonenshein
    • 1
  1. 1.Department of BiochemistryBoston University Medical SchoolBostonUSA

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