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. 1987 Jul;80(1):101–106. doi: 10.1172/JCI113034

Expression of c-myc proto-oncogene in normal human lymphocytes. Regulation by transcriptional and posttranscriptional mechanisms.

J C Reed, J D Alpers, P C Nowell
PMCID: PMC442207  PMID: 3496359

Abstract

Aberrant expression of the c-myc gene results from nonrandom chromosomal translocations involving the transcriptionally active antigen receptor gene loci, in particular lymphocytic leukemias and lymphomas, and is believed to contribute to the etiology of these neoplasms. In addition to its expression in abnormal lymphocytes, increased accumulation of c-myc mRNA occurs rapidly in normal B- and T-lymphocytes after stimulation with appropriate mitogens. The mechanisms that mediate these mitogen-induced elevations in c-myc mRNA levels, however, have not been determined for normal B and T cells. By using enriched populations of B- and T-lymphocytes obtained from freshly isolated human tonsils and stimulated with Staphylococcus-A or with phytohemagglutinin, respectively, we observed marked elevations (20-40-fold) in the steady state levels of accumulated c-myc messenger RNA (mRNA) within 1 h of exposure of cells to mitogens; modest increases (three- to fivefold) in the relative rate of transcription of the c-myc gene through protein synthesis-independent (cycloheximide-insensitive) mechanisms; and rapid rates of degradation of mature c-myc mRNAs through protein synthesis-dependent (cycloheximide-sensitive) mechanisms. These findings corroborate previous studies in other cell types and provide evidence for both transcriptional and posttranscriptional control of c-myc proto-oncogene expression in normal human lymphocytes.

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Selected References

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  1. Armelin H. A., Armelin M. C., Kelly K., Stewart T., Leder P., Cochran B. H., Stiles C. D. Functional role for c-myc in mitogenic response to platelet-derived growth factor. Nature. 1984 Aug 23;310(5979):655–660. doi: 10.1038/310655a0. [DOI] [PubMed] [Google Scholar]
  2. Bentley D. L., Groudine M. A block to elongation is largely responsible for decreased transcription of c-myc in differentiated HL60 cells. Nature. 1986 Jun 12;321(6071):702–706. doi: 10.1038/321702a0. [DOI] [PubMed] [Google Scholar]
  3. Blanchard J. M., Piechaczyk M., Dani C., Chambard J. C., Franchi A., Pouyssegur J., Jeanteur P. c-myc gene is transcribed at high rate in G0-arrested fibroblasts and is post-transcriptionally regulated in response to growth factors. Nature. 1985 Oct 3;317(6036):443–445. doi: 10.1038/317443a0. [DOI] [PubMed] [Google Scholar]
  4. Bolivar F., Backman K. Plasmids of Escherichia coli as cloning vectors. Methods Enzymol. 1979;68:245–267. doi: 10.1016/0076-6879(79)68018-7. [DOI] [PubMed] [Google Scholar]
  5. Cleveland D. W., Lopata M. A., MacDonald R. J., Cowan N. J., Rutter W. J., Kirschner M. W. Number and evolutionary conservation of alpha- and beta-tubulin and cytoplasmic beta- and gamma-actin genes using specific cloned cDNA probes. Cell. 1980 May;20(1):95–105. doi: 10.1016/0092-8674(80)90238-x. [DOI] [PubMed] [Google Scholar]
  6. Corcoran L. M., Adams J. M., Dunn A. R., Cory S. Murine T lymphomas in which the cellular myc oncogene has been activated by retroviral insertion. Cell. 1984 May;37(1):113–122. doi: 10.1016/0092-8674(84)90306-4. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Darzynkiewicz Z., Traganos F., Sharpless T., Melamed M. R. Lymphocyte stimulation: a rapid multiparameter analysis. Proc Natl Acad Sci U S A. 1976 Aug;73(8):2881–2884. doi: 10.1073/pnas.73.8.2881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Erikson J., Finger L., Sun L., ar-Rushdi A., Nishikura K., Minowada J., Finan J., Emanuel B. S., Nowell P. C., Croce C. M. Deregulation of c-myc by translocation of the alpha-locus of the T-cell receptor in T-cell leukemias. Science. 1986 May 16;232(4752):884–886. doi: 10.1126/science.3486470. [DOI] [PubMed] [Google Scholar]
  10. Gonzalez I. L., Gorski J. L., Campen T. J., Dorney D. J., Erickson J. M., Sylvester J. E., Schmickel R. D. Variation among human 28S ribosomal RNA genes. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7666–7670. doi: 10.1073/pnas.82.22.7666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Goyette M., Petropoulos C. J., Shank P. R., Fausto N. Regulated transcription of c-Ki-ras and c-myc during compensatory growth of rat liver. Mol Cell Biol. 1984 Aug;4(8):1493–1498. doi: 10.1128/mcb.4.8.1493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Hannam-Harris A. C., Taylor D. S., Nowell P. C. Cyclosporin A directly inhibits human B-cell proliferation by more than a single mechanism. J Leukoc Biol. 1985 Aug;38(2):231–239. doi: 10.1002/jlb.38.2.231. [DOI] [PubMed] [Google Scholar]
  14. Hayward W. S., Neel B. G., Astrin S. M. Activation of a cellular onc gene by promoter insertion in ALV-induced lymphoid leukosis. Nature. 1981 Apr 9;290(5806):475–480. doi: 10.1038/290475a0. [DOI] [PubMed] [Google Scholar]
  15. Kaczmarek L., Hyland J. K., Watt R., Rosenberg M., Baserga R. Microinjected c-myc as a competence factor. Science. 1985 Jun 14;228(4705):1313–1315. doi: 10.1126/science.4001943. [DOI] [PubMed] [Google Scholar]
  16. Kao H. T., Nevins J. R. Transcriptional activation and subsequent control of the human heat shock gene during adenovirus infection. Mol Cell Biol. 1983 Nov;3(11):2058–2065. doi: 10.1128/mcb.3.11.2058. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Knight E., Jr, Anton E. D., Fahey D., Friedland B. K., Jonak G. J. Interferon regulates c-myc gene expression in Daudi cells at the post-transcriptional level. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1151–1154. doi: 10.1073/pnas.82.4.1151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Krönke M., Leonard W. J., Depper J. M., Greene W. C. Sequential expression of genes involved in human T lymphocyte growth and differentiation. J Exp Med. 1985 Jun 1;161(6):1593–1598. doi: 10.1084/jem.161.6.1593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lacy J., Sarkar S. N., Summers W. C. Induction of c-myc expression in human B lymphocytes by B-cell growth factor and anti-immunoglobulin. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1458–1462. doi: 10.1073/pnas.83.5.1458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Meister R. K., Hulman S. E., Johnson L. F. Rapid changes in poly (A)(+) mRNA content in growth stimulated fibroblasts following perturbations in protein synthesis. J Cell Physiol. 1979 Sep;100(3):531–538. doi: 10.1002/jcp.1041000315. [DOI] [PubMed] [Google Scholar]
  22. Nepveu A., Fahrlander P. D., Yang J. Q., Marcu K. B. Amplification and altered expression of the c-myc oncogene in A-MuLV-transformed fibroblasts. Nature. 1985 Oct 3;317(6036):440–443. doi: 10.1038/317440a0. [DOI] [PubMed] [Google Scholar]
  23. Nepveu A., Marcu K. B. Intragenic pausing and anti-sense transcription within the murine c-myc locus. EMBO J. 1986 Nov;5(11):2859–2865. doi: 10.1002/j.1460-2075.1986.tb04580.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nowell P. C., Croce C. M. Chromosomes, genes, and cancer. Am J Pathol. 1986 Oct;125(1):7–15. [PMC free article] [PubMed] [Google Scholar]
  25. Persson H., Leder P. Nuclear localization and DNA binding properties of a protein expressed by human c-myc oncogene. Science. 1984 Aug 17;225(4663):718–721. doi: 10.1126/science.6463648. [DOI] [PubMed] [Google Scholar]
  26. Piechaczyk M., Yang J. Q., Blanchard J. M., Jeanteur P., Marcu K. B. Posttranscriptional mechanisms are responsible for accumulation of truncated c-myc RNAs in murine plasma cell tumors. Cell. 1985 Sep;42(2):589–597. doi: 10.1016/0092-8674(85)90116-3. [DOI] [PubMed] [Google Scholar]
  27. Reed J. C., Alpers J. D., Nowell P. C., Hoover R. G. Sequential expression of protooncogenes during lectin-stimulated mitogenesis of normal human lymphocytes. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3982–3986. doi: 10.1073/pnas.83.11.3982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Reed J. C., Sabath D. E., Hoover R. G., Prystowsky M. B. Recombinant interleukin 2 regulates levels of c-myc mRNA in a cloned murine T lymphocyte. Mol Cell Biol. 1985 Dec;5(12):3361–3368. doi: 10.1128/mcb.5.12.3361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Reed J. C., Tadmori W., Kamoun M., Koretzky G., Nowell P. C. Suppression of interleukin 2 receptor acquisition by monoclonal antibodies recognizing the 50 KD protein associated with the sheep erythrocyte receptor on human T lymphocytes. J Immunol. 1985 Mar;134(3):1631–1639. [PubMed] [Google Scholar]
  30. Schwab M., Ramsay G., Alitalo K., Varmus H. E., Bishop J. M., Martinsson T., Levan G., Levan A. Amplification and enhanced expression of the c-myc oncogene in mouse SEWA tumour cells. Nature. 1985 May 23;315(6017):345–347. doi: 10.1038/315345a0. [DOI] [PubMed] [Google Scholar]
  31. Studzinski G. P., Brelvi Z. S., Feldman S. C., Watt R. A. Participation of c-myc protein in DNA synthesis of human cells. Science. 1986 Oct 24;234(4775):467–470. doi: 10.1126/science.3532322. [DOI] [PubMed] [Google Scholar]
  32. Thompson C. B., Challoner P. B., Neiman P. E., Groudine M. Expression of the c-myb proto-oncogene during cellular proliferation. 1986 Jan 30-Feb 5Nature. 319(6052):374–380. doi: 10.1038/319374a0. [DOI] [PubMed] [Google Scholar]
  33. ar-Rushdi A., Nishikura K., Erikson J., Watt R., Rovera G., Croce C. M. Differential expression of the translocated and the untranslocated c-myc oncogene in Burkitt lymphoma. Science. 1983 Oct 28;222(4622):390–393. doi: 10.1126/science.6414084. [DOI] [PubMed] [Google Scholar]

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