Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1986 May 1;163(5):1292–1307. doi: 10.1084/jem.163.5.1292

Oncogene expression in autoimmune and normal peripheral blood mononuclear cells

PMCID: PMC2188108  PMID: 3701256

Abstract

PBMC from patients with autoimmune diseases and from normal controls were studied for the expression of several cellular oncogenes. Gene expression was assessed by Northern blot analysis of poly(A)+ RNA obtained from leukapheresis samples. Patients with SLE expressed significantly more c-myc protooncogene RNA than did normal controls. Increased expression of the N-ras protooncogene was found in that subset of patients whose autoimmune disease was very active. Cells from individuals with SLE, but not from those with other autoimmune illnesses, showed significantly decreased levels of the c-myb and c-fos protooncogenes. To examine the implications of these findings, B and T cells were purified from apheresis samples donated by normal volunteers. When mitogen was used to activate the B cells in vitro, their pattern of protooncogene expression changed to resemble that found in freshly isolated cells from lupus patients. These results suggest that the differences detected in the expression of protooncogenes by patients with SLE may be due to the abnormal activation of their B cells in vivo. The pattern of protooncogene expression found in patients with other autoimmune illnesses is consistent with the activation of additional cell types in those diseases.

Full Text

The Full Text of this article is available as a PDF (1.6 MB).

Selected References

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

  1. Arnett F. C., Shulman L. E. Studies in familial systemic lupus erythematosus. Medicine (Baltimore) 1976 Jul;55(4):313–322. doi: 10.1097/00005792-197607000-00003. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Blaese R. M., Grayson J., Steinberg A. D. Increased immunoglobulin-secreting cells in the blood of patients with active systemic lupus erythematosus. Am J Med. 1980 Sep;69(3):345–350. doi: 10.1016/0002-9343(80)90003-0. [DOI] [PubMed] [Google Scholar]
  4. Campisi J., Gray H. E., Pardee A. B., Dean M., Sonenshein G. E. Cell-cycle control of c-myc but not c-ras expression is lost following chemical transformation. Cell. 1984 Feb;36(2):241–247. doi: 10.1016/0092-8674(84)90217-4. [DOI] [PubMed] [Google Scholar]
  5. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  6. Cooper G. M. Structural and functional analysis of ras and Blym oncogenes. Curr Top Microbiol Immunol. 1984;113:34–36. doi: 10.1007/978-3-642-69860-6_7. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. Ginsburg W. W., Finkelman F. D., Lipsky P. E. Circulating and pokeweed mitogen-induced immunoglobulin-secreting cells in systemic lupus erythematosus. Clin Exp Immunol. 1979 Jan;35(1):76–88. [PMC free article] [PubMed] [Google Scholar]
  10. Glinski W., Gershwin M. E., Budman D. R., Steinberg A. D. Study of lymphocyte subpopulations in normal humans and patients with systemic lupus erythematosus by fractionation of peripheral blood lymphocytes on a discontinuous Ficoll gradient. Clin Exp Immunol. 1976 Nov;26(2):228–238. [PMC free article] [PubMed] [Google Scholar]
  11. Glisin V., Crkvenjakov R., Byus C. Ribonucleic acid isolated by cesium chloride centrifugation. Biochemistry. 1974 Jun 4;13(12):2633–2637. doi: 10.1021/bi00709a025. [DOI] [PubMed] [Google Scholar]
  12. Gonda T. J., Metcalf D. Expression of myb, myc and fos proto-oncogenes during the differentiation of a murine myeloid leukaemia. Nature. 1984 Jul 19;310(5974):249–251. doi: 10.1038/310249a0. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Honda M., Steinberg A. D. Effects of prostaglandin E2 on responses of T-cell subsets to mitogen and autologous non-T-cell stimulation. Clin Immunol Immunopathol. 1984 Oct;33(1):111–122. doi: 10.1016/0090-1229(84)90297-6. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Kelly K., Siebenlist U. The role of c-myc in the proliferation of normal and neoplastic cells. J Clin Immunol. 1985 Mar;5(2):65–77. doi: 10.1007/BF00915003. [DOI] [PubMed] [Google Scholar]
  17. Klein G. Specific chromosomal translocations and the genesis of B-cell-derived tumors in mice and men. Cell. 1983 Feb;32(2):311–315. doi: 10.1016/0092-8674(83)90449-x. [DOI] [PubMed] [Google Scholar]
  18. Krishan A. Rapid flow cytofluorometric analysis of mammalian cell cycle by propidium iodide staining. J Cell Biol. 1975 Jul;66(1):188–193. doi: 10.1083/jcb.66.1.188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Marshall C. Functions of ras oncogenes. Nature. 1984 Aug 9;310(5977):448–448. doi: 10.1038/310448a0. [DOI] [PubMed] [Google Scholar]
  20. Mountz J. D., Mushinski J. F., Mark G. E., Steinberg A. D. Oncogene expression in autoimmune mice. J Mol Cell Immunol. 1985;2(3):121–131. [PubMed] [Google Scholar]
  21. Mountz J. D., Steinberg A. D., Klinman D. M., Smith H. R., Mushinski J. F. Autoimmunity and increased c-myb transcription. Science. 1984 Nov 30;226(4678):1087–1089. doi: 10.1126/science.6494925. [DOI] [PubMed] [Google Scholar]
  22. Mushinski J. F., Blattner F. R., Owens J. D., Finkelman F. D., Kessler S. W., Fitzmaurice L., Potter M., Tucker P. W. Mouse immunoglobulin D: construction and characterization of a cloned delta chain cDNA. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7405–7409. doi: 10.1073/pnas.77.12.7405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mushinski J. F., Potter M., Bauer S. R., Reddy E. P. DNA rearrangement and altered RNA expression of the c-myb oncogene in mouse plasmacytoid lymphosarcomas. Science. 1983 May 20;220(4599):795–798. doi: 10.1126/science.6687762. [DOI] [PubMed] [Google Scholar]
  24. Müller R., Bravo R., Burckhardt J., Curran T. Induction of c-fos gene and protein by growth factors precedes activation of c-myc. Nature. 1984 Dec 20;312(5996):716–720. doi: 10.1038/312716a0. [DOI] [PubMed] [Google Scholar]
  25. Polsky F., Edgell M. H., Seidman J. G., Leder P. High capacity gel preparative electrophoresis for purification of fragments of genomic DNA. Anal Biochem. 1978 Jul 1;87(2):397–410. doi: 10.1016/0003-2697(78)90689-9. [DOI] [PubMed] [Google Scholar]
  26. Raveche E. S., Alabaster O., Tjio J. H., Taurog J., Steinberg A. D. Analysis of NZB hyperdiploid spleen cells. J Immunol. 1981 Jan;126(1):154–160. [PubMed] [Google Scholar]
  27. Reinersten J. L., Klippel J. H., Johnson A. H., Steinberg A. D., Decker J. L., Mann D. L. Family studies of B lymphocyte alloantigens in systemic lupus erythematosus. J Rheumatol. 1982 Mar-Apr;9(2):253–262. [PubMed] [Google Scholar]
  28. Sefton B. M., Hunter T., Raschke W. C. Evidence that the Abelson virus protein functions in vivo as a protein kinase that phosphorylates tyrosine. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1552–1556. doi: 10.1073/pnas.78.3.1552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Shapiro H. M. Flow cytometric estimation of DNA and RNA content in intact cells stained with Hoechst 33342 and pyronin Y. Cytometry. 1981 Nov;2(3):143–150. doi: 10.1002/cyto.990020302. [DOI] [PubMed] [Google Scholar]
  30. Slamon D. J., deKernion J. B., Verma I. M., Cline M. J. Expression of cellular oncogenes in human malignancies. Science. 1984 Apr 20;224(4646):256–262. doi: 10.1126/science.6538699. [DOI] [PubMed] [Google Scholar]
  31. Smith H. R., Steinberg A. D. Autoimmunity--a perspective. Annu Rev Immunol. 1983;1:175–210. doi: 10.1146/annurev.iy.01.040183.001135. [DOI] [PubMed] [Google Scholar]
  32. Srinivasan A., Reddy E. P., Aaronson S. A. Abelson murine leukemia virus: molecular cloning of infectious integrated proviral DNA. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2077–2081. doi: 10.1073/pnas.78.4.2077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Steinberg A. D. Recent advances on the mechanisms and genetic aspects of lupus erythematosus. Adv Nephrol Necker Hosp. 1985;14:305–332. [PubMed] [Google Scholar]
  34. Steinberg B. J., Smathers P. A., Frederiksen K., Steinberg A. D. Ability of the xid gene to prevent autoimmunity in (NZB X NZW)F1 mice during the course of their natural history, after polyclonal stimulation, or following immunization with DNA. J Clin Invest. 1982 Sep;70(3):587–597. doi: 10.1172/JCI110651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Taparowsky E., Shimizu K., Goldfarb M., Wigler M. Structure and activation of the human N-ras gene. Cell. 1983 Sep;34(2):581–586. doi: 10.1016/0092-8674(83)90390-2. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. Thompson C. B., Challoner P. B., Neiman P. E., Groudine M. Levels of c-myc oncogene mRNA are invariant throughout the cell cycle. 1985 Mar 28-Apr 3Nature. 314(6009):363–366. doi: 10.1038/314363a0. [DOI] [PubMed] [Google Scholar]
  38. Traganos F., Darzynkiewicz Z., Sharpless T., Melamed M. R. Simultaneous staining of ribonucleic and deoxyribonucleic acids in unfixed cells using acridine orange in a flow cytofluorometric system. J Histochem Cytochem. 1977 Jan;25(1):46–56. doi: 10.1177/25.1.64567. [DOI] [PubMed] [Google Scholar]
  39. Traganos F., Darzynkiewicz Z., Sharpless T., Melamed M. R. Simultaneous staining of ribonucleic and deoxyribonucleic acids in unfixed cells using acridine orange in a flow cytofluorometric system. J Histochem Cytochem. 1977 Jan;25(1):46–56. doi: 10.1177/25.1.64567. [DOI] [PubMed] [Google Scholar]
  40. Westin E. H., Gallo R. C., Arya S. K., Eva A., Souza L. M., Baluda M. A., Aaronson S. A., Wong-Staal F. Differential expression of the amv gene in human hematopoietic cells. Proc Natl Acad Sci U S A. 1982 Apr;79(7):2194–2198. doi: 10.1073/pnas.79.7.2194. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES