Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1983 Aug;80(15):4822–4826. doi: 10.1073/pnas.80.15.4822

Differential expression of the normal and of the translocated human c-myc oncogenes in B cells.

K Nishikura, A ar-Rushdi, J Erikson, R Watt, G Rovera, C M Croce
PMCID: PMC384137  PMID: 6308654

Abstract

We have investigated whether the translocated and the untranslocated human c-myc oncogenes of Burkitt lymphoma cells are equally or differentially expressed in host mouse B cells. The human c-myc mRNA levels in somatic cell hybrids between mouse plasmacytoma cells and Burkitt lymphoma cells with either the t(8;14) or the t(2;8) chromosome translocation were determined by using the nuclease S1 protection procedure. Although both the human parental lines and the hybrid cells carrying the translocated c-muc oncogene expressed high levels of human specific c-myc transcripts, the hybrid cells carrying the untranslocated c-myc gene on normal chromosome 8 did not contain human specific c-myc mRNA. These results suggest that the translocated human c-myc oncogene has escaped the normal transcriptional control to which the untranslocated c-myc gene remains subjected. This interpretation is also supported by the finding that the expression of the c-myc genes of lymphoblastoid cells and of HL-60 promyelocytic leukemia cells are repressed when they are transferred into a mouse plasmacytoma background. The ability of the translocated c-myc oncogene to escape the normal transcriptional control occurring in B cells may be important for the expression of B cell neoplasia in mouse and man. We have also transferred the Burkitt 14q+ chromosome carrying a translocated c-myc oncogene into mouse LM-TK- fibroblasts and studied the levels of human c-myc transcripts in the hybrids. Because the levels of human c-myc transcripts in the fibroblast hybrids are dramatically decreased in comparison to the plasmacytoma hybrids, we conclude that the levels of transcripts of the translocated c-myc oncogene depend on the differentiated state of the cells harboring the translocated chromosome.

Full text

PDF
4822

Images in this article

4824Image
on p.4824
4824Image
on p.4824
4824Image
on p.4824
4825Image
on p.4825
4825Image
on p.4825
4825Image
on p.4825
4825Image
on p.4825

Selected References

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

  1. Bernheim A., Berger R., Lenoir G. Cytogenetic studies on African Burkitt's lymphoma cell lines: t(8;14), t(2;8) and t(8;22) translocations. Cancer Genet Cytogenet. 1981 Jun;3(4):307–315. doi: 10.1016/0165-4608(81)90039-x. [DOI] [PubMed] [Google Scholar]
  2. Bobrow M., Cross J. Differential staining of human and mouse chromosomes in interspecific cell hybrids. Nature. 1974 Sep 6;251(5470):77–79. doi: 10.1038/251077a0. [DOI] [PubMed] [Google Scholar]
  3. Colby W. W., Chen E. Y., Smith D. H., Levinson A. D. Identification and nucleotide sequence of a human locus homologous to the v-myc oncogene of avian myelocytomatosis virus MC29. Nature. 1983 Feb 24;301(5902):722–725. doi: 10.1038/301722a0. [DOI] [PubMed] [Google Scholar]
  4. Collins S. J., Gallo R. C., Gallagher R. E. Continuous growth and differentiation of human myeloid leukaemic cells in suspension culture. Nature. 1977 Nov 24;270(5635):347–349. doi: 10.1038/270347a0. [DOI] [PubMed] [Google Scholar]
  5. Croce C. M., Shander M., Martinis J., Cicurel L., D'Ancona G. G., Dolby T. W., Koprowski H. Chromosomal location of the genes for human immunoglobulin heavy chains. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3416–3419. doi: 10.1073/pnas.76.7.3416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DUBBS D. R., KIT S. EFFECT OF HALOGENATED PYRIMIDINES AND THYMIDINE ON GROWTH OF L-CELLS AND A SUBLINE LACKING THYMIDINE KINASE. Exp Cell Res. 1964 Jan;33:19–28. doi: 10.1016/s0014-4827(64)81006-5. [DOI] [PubMed] [Google Scholar]
  7. Dalla-Favera R., Bregni M., Erikson J., Patterson D., Gallo R. C., Croce C. M. Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7824–7827. doi: 10.1073/pnas.79.24.7824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dalla-Favera R., Franchini G., Martinotti S., Wong-Staal F., Gallo R. C., Croce C. M. Chromosomal assignment of the human homologues of feline sarcoma virus and avian myeloblastosis virus onc genes. Proc Natl Acad Sci U S A. 1982 Aug;79(15):4714–4717. doi: 10.1073/pnas.79.15.4714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dalla-Favera R., Gallo R. C., Giallongo A., Croce C. M. Chromosomal localization of the human homolog (c-sis) of the simian sarcoma virus onc gene. Science. 1982 Nov 12;218(4573):686–688. doi: 10.1126/science.6291150. [DOI] [PubMed] [Google Scholar]
  10. Dalla-Favera R., Martinotti S., Gallo R. C., Erikson J., Croce C. M. Translocation and rearrangements of the c-myc oncogene locus in human undifferentiated B-cell lymphomas. Science. 1983 Feb 25;219(4587):963–967. doi: 10.1126/science.6401867. [DOI] [PubMed] [Google Scholar]
  11. Dalla-Favera R., Wong-Staal F., Gallo R. C. Onc gene amplification in promyelocytic leukaemia cell line HL-60 and primary leukaemic cells of the same patient. Nature. 1982 Sep 2;299(5878):61–63. doi: 10.1038/299061a0. [DOI] [PubMed] [Google Scholar]
  12. Erikson J., Croce C. M. Secretion of human immunoglobulins by mouse myeloma x Daudi somatic cell hybrids. Eur J Immunol. 1982 Aug;12(8):697–701. doi: 10.1002/eji.1830120814. [DOI] [PubMed] [Google Scholar]
  13. Erikson J., Finan J., Nowell P. C., Croce C. M. Translocation of immunoglobulin VH genes in Burkitt lymphoma. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5611–5615. doi: 10.1073/pnas.79.18.5611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Erikson J., Martinis J., Croce C. M. Assignment of the genes for human lambda immunoglobulin chains to chromosome 22. Nature. 1981 Nov 12;294(5837):173–175. doi: 10.1038/294173a0. [DOI] [PubMed] [Google Scholar]
  15. Erikson J., ar-Rushdi A., Drwinga H. L., Nowell P. C., Croce C. M. Transcriptional activation of the translocated c-myc oncogene in burkitt lymphoma. Proc Natl Acad Sci U S A. 1983 Feb;80(3):820–824. doi: 10.1073/pnas.80.3.820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Köhler G., Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495–497. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
  17. Lenoir G. M., Preud'homme J. L., Bernheim A., Berger R. Correlation between immunoglobulin light chain expression and variant translocation in Burkitt's lymphoma. Nature. 1982 Jul 29;298(5873):474–476. doi: 10.1038/298474a0. [DOI] [PubMed] [Google Scholar]
  18. Malcolm S., Barton P., Murphy C., Ferguson-Smith M. A., Bentley D. L., Rabbitts T. H. Localization of human immunoglobulin kappa light chain variable region genes to the short arm of chromosome 2 by in situ hybridization. Proc Natl Acad Sci U S A. 1982 Aug;79(16):4957–4961. doi: 10.1073/pnas.79.16.4957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Maniatis T., Jeffrey A., van deSande H. Chain length determination of small double- and single-stranded DNA molecules by polyacrylamide gel electrophoresis. Biochemistry. 1975 Aug 26;14(17):3787–3794. doi: 10.1021/bi00688a010. [DOI] [PubMed] [Google Scholar]
  20. Manolov G., Manolova Y. Marker band in one chromosome 14 from Burkitt lymphomas. Nature. 1972 May 5;237(5349):33–34. doi: 10.1038/237033a0. [DOI] [PubMed] [Google Scholar]
  21. Marcu K. B., Harris L. J., Stanton L. W., Erikson J., Watt R., Croce C. M. Transcriptionally active c-myc oncogene is contained within NIARD, a DNA sequence associated with chromosome translocations in B-cell neoplasia. Proc Natl Acad Sci U S A. 1983 Jan;80(2):519–523. doi: 10.1073/pnas.80.2.519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Margulies D. H., Kuehl W. M., Scharff M. D. Somatic cell hybridization of mouse myeloma cells. Cell. 1976 Jul;8(3):405–415. doi: 10.1016/0092-8674(76)90153-7. [DOI] [PubMed] [Google Scholar]
  23. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  24. Miyoshi I., Hiraki S., Kimura I., Miyamoto K., Sato J. 2/8 translocation in a Japanese Burkitt's lymphoma. Experientia. 1979 Jun 15;35(6):742–743. doi: 10.1007/BF01968217. [DOI] [PubMed] [Google Scholar]
  25. Neel B. G., Jhanwar S. C., Chaganti R. S., Hayward W. S. Two human c-onc genes are located on the long arm of chromosome 8. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7842–7846. doi: 10.1073/pnas.79.24.7842. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Seabright M. A rapid banding technique for human chromosomes. Lancet. 1971 Oct 30;2(7731):971–972. doi: 10.1016/s0140-6736(71)90287-x. [DOI] [PubMed] [Google Scholar]
  27. Sharp P. A., Berk A. J., Berget S. M. Transcription maps of adenovirus. Methods Enzymol. 1980;65(1):750–768. doi: 10.1016/s0076-6879(80)65071-x. [DOI] [PubMed] [Google Scholar]
  28. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  29. Stanton L. W., Watt R., Marcu K. B. Translocation, breakage and truncated transcripts of c-myc oncogene in murine plasmacytomas. Nature. 1983 Jun 2;303(5916):401–406. doi: 10.1038/303401a0. [DOI] [PubMed] [Google Scholar]
  30. Swan D. C., McBride O. W., Robbins K. C., Keithley D. A., Reddy E. P., Aaronson S. A. Chromosomal mapping of the simian sarcoma virus onc gene analogue in human cells. Proc Natl Acad Sci U S A. 1982 Aug;79(15):4691–4695. doi: 10.1073/pnas.79.15.4691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. 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]
  32. Watson R., Oskarsson M., Vande Woude G. F. Human DNA sequence homologous to the transforming gene (mos) of Moloney murine sarcoma virus. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4078–4082. doi: 10.1073/pnas.79.13.4078. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Weaver R. F., Weissmann C. Mapping of RNA by a modification of the Berk-Sharp procedure: the 5' termini of 15 S beta-globin mRNA precursor and mature 10 s beta-globin mRNA have identical map coordinates. Nucleic Acids Res. 1979 Nov 10;7(5):1175–1193. doi: 10.1093/nar/7.5.1175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Zech L., Haglund U., Nilsson K., Klein G. Characteristic chromosomal abnormalities in biopsies and lymphoid-cell lines from patients with Burkitt and non-Burkitt lymphomas. Int J Cancer. 1976 Jan 15;17(1):47–56. doi: 10.1002/ijc.2910170108. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES