Investigation of Aberrant Translational Control of c-myc in Cell Lines Derived from Patients with Multiple Myeloma

  • A. E. Willis
  • F. E. M. Paulin
  • M. J. West
  • R. L. Whitney
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 224)


In cell lines derived from patients with multiple myeloma (MM) we have found an elevation in the amount of the c-myc protein which is not accompanied by an increase in the level of mRNA or a change in the half-life of the protein. There is a 3.4 fold enhancement in the degree of association of the c-myc message with polysomes. This is not accompanied by an alteration in polysome size or a change in the transit time of the c-myc mRNA on the polysomes thus suggesting that there is an increase in the degree of mobilisation of the c-myc message. Sequencing of the c-myc 5’UTR has revealed the presence of a mutation in all the MM cell lines studied and we demonstrate that this mutation causes altered binding of cellular proteins to this RNA species.


Multiple Myeloma Electrophoretic Mobility Shift Assay Mutant Sequence Control Cell Line Wild Type Sequence 
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. Barker HF, Hamilton MS, Ball J, Drew M and Franklin IM. (1992). Mutiple myeloma: The biology of the malignant plasma cell. British Journal Of Haematology., 81: 331–335.PubMedCrossRefGoogle Scholar
  2. Caligaris-Cappio M, Gaidano M, Gaboli M, Schena AS, and Marchisio C. (1991) The role of bone marrow stromal cells in the growth of human mutiple myeloma. Blood:77 2688–2693PubMedGoogle Scholar
  3. Carter A, Merchav I, Silvian-Draxler I and Tatarsky I. (1990) The role of inerleukin-1 and tumour necrosis factor alpha in human multiple myeloma. Blood 74:424–431.Google Scholar
  4. Corradini P., Ladetto M, Voena C, Paulumbo A, Inghirami G, Knowles DM, Boccadoro M and Pilleri A., (1993) Mutational Activation of N- and K-ras Oncogenes in Plasma Cell Dyscrasias. Blood 81: 2708–2713.PubMedGoogle Scholar
  5. Darveau A, Pelletier J and Sonenberg N. (1985) Differenital efficiences of in vitro translation of mouse c-myc transcripts differing in the 5’ untranslated region. Proc.Natl.Acad. Sci..USA., 82:2315–2319PubMedCentralPubMedCrossRefGoogle Scholar
  6. Gazin C, Dupont de Dinechin S, Hampe A, Masson J-M, Martin P, Stehelin D and Galibert F. (1984). Nucleotide sequence of the human c-myc locis:provocative open reading frame within the first exon. EMBO. J., 3:383–387.PubMedCentralPubMedGoogle Scholar
  7. Gray N and Hentze M. (1994). Regulation of protein synthesis by mRNA structure. Molecular Biology Reports, 19: 195–200.PubMedCrossRefGoogle Scholar
  8. Hann SR and Eisenman RN. (1984). Proteins expressed by the c-myc oncogene in lymphomas of human and avian origin. Mol.Cell Biol., 4: 11. 2486–2497.PubMedCentralPubMedGoogle Scholar
  9. Hiltzer J, Martinez-Valdez D, Berghasel M, Minden M and Messener H., (1991) Role of Interleukin-6 in the proliferation of human multiple myeloma cell lines oci-my 1 to 7 established from patients with advanced Stage of the disease. Blood 8:1996–2004.Google Scholar
  10. Hollis GF, Gazdar AF, Bertness V and Kirsch JR. (1988). Complex translocational disrupts c-myc regulation in a human plasma cell myeloma. Mol. Cell. Biol., 8: 124–129.PubMedCentralPubMedGoogle Scholar
  11. Hershey JWB (1991). Translational control in mammalian cells. Annu. Rev. Biochem., 60:717–755.PubMedCrossRefGoogle Scholar
  12. Lewis J and MacKenzie M (1984). Non-random chromosomal aberrations associated with multiple myeloma. Haematology Oncol., 2:307–317.CrossRefGoogle Scholar
  13. Neivizky R, Siegel D and Michaeli J. (1993). Biology and treatment of multiple myeloma. Blood, 7: 24–33CrossRefGoogle Scholar
  14. Neri A, Murphy JP, Gro L, Ferrero D, Tarella C, Baldini L and Dalla-Favera R. (1989). RAS Oncogene mutations in multiple myeloma J. Exp. Med., 170: 1715–1722.PubMedCrossRefGoogle Scholar
  15. Neri A, Baldini L, Trecca D, Gro L, Polli E and Maiolo AT. (1993). p53 Gene mutations in multiple myeloma are associated with advanced forms of malignancy. Blood, 81: 128–135.PubMedGoogle Scholar
  16. Portier M, Moles JP, Mazars G, Jeanteur P, Bataille R and Theillet C. (1992). p53 and RAS gene mutations in multiple myeloma. Oncogene, 7: 2539–2543.PubMedGoogle Scholar
  17. Parkin N, Darveau A, Nicholson R and Sonenberg N. (1988). cis-acting translational affects of the 5’ non-coding region of the c-myc mRNA Mol.Cell.Biol., 8: 2875–2883.PubMedCentralPubMedGoogle Scholar
  18. Selvanayagam PM, Blick F, Narni P, van Tuinen DH, Ledbetter R, Alexanian GF, Saunders G and Barlogie B. (1988). Alteration and abnormal expression of the c-myc oncogene in human multiple myeloma. Blood, 71, 30–35.PubMedGoogle Scholar
  19. Sullivan NF, Willis AE, Moore JP and Lindahl T. (1989). High levels of the c-myc protein in cell lines of Bloom’s syndrome origin. Oncogene 4: 1509–1511.PubMedGoogle Scholar
  20. Theodorakis NG, Banerji SS and Morimoto RI. (1988). HSP70 mRNA Translation in chicken reticulocytes is regulated at the level of elongation. J. Biol. Chem., 263:14579–14585.PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • A. E. Willis
    • 1
  • F. E. M. Paulin
    • 1
  • M. J. West
    • 1
  • R. L. Whitney
    • 1
  1. 1.Department of BiochemistryUniversity of LeicesterLeicesterUK

Personalised recommendations