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. 1988 Apr;85(8):2638–2642. doi: 10.1073/pnas.85.8.2638

Phorbol ester-induced terminal differentiation is inhibited in human U-937 monoblastic cells expressing a v-myc oncogene.

L G Larsson 1, I Ivhed 1, M Gidlund 1, U Pettersson 1, B Vennström 1, K Nilsson 1
PMCID: PMC280053  PMID: 3357885

Abstract

Induction of differentiation of the human monoblastic cell line U-937 in vitro by several physiologic and nonphysiologic inducers is accompanied by a rapid decrease in expression of MYC, the endogenous human myc protooncogene. To investigate whether this reduction is a prerequisite for terminal differentiation, we introduced a constitutively expressed v-myc gene into U-937 cells. The results show that constitutive expression of an avian v-myc oncogene does not interfere with phorbol 12-myristate 13-acetate-induced differentiation of U-937 cells early after stimulation. However, after 24 hr the differentiation process is reversed, as judged by a full recovery of the proliferative capacity and reexpression of the immature phenotype, within the next 2-4 days. We conclude that the terminal stage of macrophage differentiation is inhibited in U-937 cells constitutively expressing a v-myc oncogene.

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Selected References

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

  1. Adams J. M., Harris A. W., Pinkert C. A., Corcoran L. M., Alexander W. S., Cory S., Palmiter R. D., Brinster R. L. The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature. 1985 Dec 12;318(6046):533–538. doi: 10.1038/318533a0. [DOI] [PubMed] [Google Scholar]
  2. Alema S., Tato F., Boettiger D. myc and src oncogenes have complementary effects on cell proliferation and expression of specific extracellular matrix components in definitive chondroblasts. Mol Cell Biol. 1985 Mar;5(3):538–544. doi: 10.1128/mcb.5.3.538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bishop J. M. The molecular genetics of cancer. Science. 1987 Jan 16;235(4786):305–311. doi: 10.1126/science.3541204. [DOI] [PubMed] [Google Scholar]
  4. Blasi E., Mathieson B. J., Varesio L., Cleveland J. L., Borchert P. A., Rapp U. R. Selective immortalization of murine macrophages from fresh bone marrow by a raf/myc recombinant murine retrovirus. Nature. 1985 Dec 19;318(6047):667–670. doi: 10.1038/318667a0. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Cone R. D., Mulligan R. C. High-efficiency gene transfer into mammalian cells: generation of helper-free recombinant retrovirus with broad mammalian host range. Proc Natl Acad Sci U S A. 1984 Oct;81(20):6349–6353. doi: 10.1073/pnas.81.20.6349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Coppola J. A., Cole M. D. Constitutive c-myc oncogene expression blocks mouse erythroleukaemia cell differentiation but not commitment. Nature. 1986 Apr 24;320(6064):760–763. doi: 10.1038/320760a0. [DOI] [PubMed] [Google Scholar]
  8. Dalla-Favera R., Gelmann E. P., Martinotti S., Franchini G., Papas T. S., Gallo R. C., Wong-Staal F. Cloning and characterization of different human sequences related to the onc gene (v-myc) of avian myelocytomatosis virus (MC29). Proc Natl Acad Sci U S A. 1982 Nov;79(21):6497–6501. doi: 10.1073/pnas.79.21.6497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dotto G. P., Gilman M. Z., Maruyama M., Weinberg R. A. c-myc and c-fos expression in differentiating mouse primary keratinocytes. EMBO J. 1986 Nov;5(11):2853–2857. doi: 10.1002/j.1460-2075.1986.tb04579.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Durban E. M., Boettiger D. Differential effects of transforming avian RNA tumor viruses on avian macrophages. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3600–3604. doi: 10.1073/pnas.78.6.3600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Einat M., Resnitzky D., Kimchi A. Close link between reduction of c-myc expression by interferon and, G0/G1 arrest. Nature. 1985 Feb 14;313(6003):597–600. doi: 10.1038/313597a0. [DOI] [PubMed] [Google Scholar]
  12. Falcone G., Tatò F., Alemà S. Distinctive effects of the viral oncogenes myc, erb, fps, and src on the differentiation program of quail myogenic cells. Proc Natl Acad Sci U S A. 1985 Jan;82(2):426–430. doi: 10.1073/pnas.82.2.426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Frykberg L., Graf T., Vennström B. The transforming activity of the chicken c-myc gene can be potentiated by mutations. Oncogene. 1987;1(4):415–422. [PubMed] [Google Scholar]
  14. Gidlund M., Orn A., Pattengale P. K., Jansson M., Wigzell H., Nilsson K. Natural killer cells kill tumour cells at a given stage of differentiation. Nature. 1981 Aug 27;292(5826):848–850. doi: 10.1038/292848a0. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Graf T., Beug H. Avian leukemia viruses: interaction with their target cells in vivo and in vitro. Biochim Biophys Acta. 1978 Nov 17;516(3):269–299. doi: 10.1016/0304-419x(78)90011-2. [DOI] [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. Klein G., Klein E. Evolution of tumours and the impact of molecular oncology. Nature. 1985 May 16;315(6016):190–195. doi: 10.1038/315190a0. [DOI] [PubMed] [Google Scholar]
  19. Lachman H. M., Skoultchi A. I. Expression of c-myc changes during differentiation of mouse erythroleukaemia cells. Nature. 1984 Aug 16;310(5978):592–594. doi: 10.1038/310592a0. [DOI] [PubMed] [Google Scholar]
  20. Larsson L. G., Gray H. E., Tötterman T., Pettersson U., Nilsson K. Drastically increased expression of MYC and FOS protooncogenes during in vitro differentiation of chronic lymphocytic leukemia cells. Proc Natl Acad Sci U S A. 1987 Jan;84(1):223–227. doi: 10.1073/pnas.84.1.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Minty A. J., Caravatti M., Robert B., Cohen A., Daubas P., Weydert A., Gros F., Buckingham M. E. Mouse actin messenger RNAs. Construction and characterization of a recombinant plasmid molecule containing a complementary DNA transcript of mouse alpha-actin mRNA. J Biol Chem. 1981 Jan 25;256(2):1008–1014. [PubMed] [Google Scholar]
  22. Moscicki R. A., Amento E. P., Krane S. M., Kurnick J. T., Colvin R. B. Modulation of surface antigens of a human monocyte cell line, U937, during incubation with T lymphocyte-conditioned medium: detection of T4 antigen and its presence on normal blood monocytes. J Immunol. 1983 Aug;131(2):743–748. [PubMed] [Google Scholar]
  23. Sachs L. Constitutive uncoupling of pathways of gene expression that control growth and differentiation in myeloid leukemia: a model for the origin and progression of malignancy. Proc Natl Acad Sci U S A. 1980 Oct;77(10):6152–6156. doi: 10.1073/pnas.77.10.6152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schneider M. D., Perryman M. B., Payne P. A., Spizz G., Roberts R., Olson E. N. Autonomous expression of c-myc in BC3H1 cells partially inhibits but does not prevent myogenic differentiation. Mol Cell Biol. 1987 May;7(5):1973–1977. doi: 10.1128/mcb.7.5.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Sundström C., Nilsson K. Establishment and characterization of a human histiocytic lymphoma cell line (U-937). Int J Cancer. 1976 May 15;17(5):565–577. doi: 10.1002/ijc.2910170504. [DOI] [PubMed] [Google Scholar]
  27. Vennstrom B., Sheiness D., Zabielski J., Bishop J. M. Isolation and characterization of c-myc, a cellular homolog of the oncogene (v-myc) of avian myelocytomatosis virus strain 29. J Virol. 1982 Jun;42(3):773–779. doi: 10.1128/jvi.42.3.773-779.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Vennström B., Kahn P., Adkins B., Enrietto P., Hayman M. J., Graf T., Luciw P. Transformation of mammalian fibroblasts and macrophages in vitro by a murine retrovirus encoding an avian v-myc oncogene. EMBO J. 1984 Dec 20;3(13):3223–3229. doi: 10.1002/j.1460-2075.1984.tb02282.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wagner E. F., Vanek M., Vennström B. Transfer of genes into embryonal carcinoma cells by retrovirus infection: efficient expression from an internal promoter. EMBO J. 1985 Mar;4(3):663–666. doi: 10.1002/j.1460-2075.1985.tb03680.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Watt R. A., Shatzman A. R., Rosenberg M. Expression and characterization of the human c-myc DNA-binding protein. Mol Cell Biol. 1985 Mar;5(3):448–456. doi: 10.1128/mcb.5.3.448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Westin E. H., Wong-Staal F., Gelmann E. P., Dalla-Favera R., Papas T. S., Lautenberger J. A., Eva A., Reddy E. P., Tronick S. R., Aaronson S. A. Expression of cellular homologues of retroviral onc genes in human hematopoietic cells. Proc Natl Acad Sci U S A. 1982 Apr;79(8):2490–2494. doi: 10.1073/pnas.79.8.2490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. von Weizsäcker F., Beug H., Graf T. Temperature-sensitive mutants of MH2 avian leukemia virus that map in the v-mil and the v-myc oncogene respectively. EMBO J. 1986 Jul;5(7):1521–1527. doi: 10.1002/j.1460-2075.1986.tb04392.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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