Skip to main content
NCBI home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1989 Oct;9(10):4515–4522. doi: 10.1128/mcb.9.10.4515

Insertional activation of N-myc by endogenous Moloney-like murine retrovirus sequences in macrophage cell lines derived from myeloma cell line-macrophage hybrids.

M Setoguchi 1, Y Higuchi 1, S Yoshida 1, N Nasu 1, Y Miyazaki 1, S Akizuki 1, S Yamamoto 1
PMCID: PMC362536  PMID: 2555695

Abstract

Hybrids formed from a myeloma cell line, NS1, and macrophages initially show myeloma properties but later, after loss of the parental macrophage genome and consequent loss of myeloma characteristics, express macrophage properties. Molecular studies demonstrated that macrophage properties in the hybridomas originate from the NS1 parental cells (M. Setoguchi, S. Yoshida, Y. Higuchi, S. Akizuki, and S. Yamamoto, Somatic Cell Mol. Genet. 14:427-438, 1988). In such hybrids, N-myc was activated by insertion of endogenous Moloney-like retrovirus sequences into mouse N-myc exon 3 when the hybrids gained macrophage properties. Interestingly, expression of N-myc took place in all aged hybrids. These results suggest that such unique insertional mutagenesis occurs in a regionally specific manner and that expression of N-myc may play a role in hematopoietic lineage conversion.

Full text

PDF
4515

Images in this article

4516Image
on p.4516
4519Image
on p.4519
4519Image
on p.4519

Selected References

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

  1. Bauer S. R., Holmes K. L., Morse H. C., 3rd, Potter M. Clonal relationship of the lymphoblastic cell line P388 to the macrophage cell line P388D1 as evidenced by immunoglobulin gene rearrangements and expression of cell surface antigens. J Immunol. 1986 Jun 15;136(12):4695–4699. [PubMed] [Google Scholar]
  2. Bosselman R. A., van Straaten F., Van Beveren C., Verma I. M., Vogt M. Analysis of the env gene of a molecularly cloned and biologically active Moloney mink cell focus-forming proviral DNA. J Virol. 1982 Oct;44(1):19–31. doi: 10.1128/jvi.44.1.19-31.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Boyd A. W., Schrader J. W. Derivation of macrophage-like lines from the pre-B lymphoma ABLS 8.1 using 5-azacytidine. Nature. 1982 Jun 24;297(5868):691–693. doi: 10.1038/297691a0. [DOI] [PubMed] [Google Scholar]
  4. Calame K., Kim S., Lalley P., Hill R., Davis M., Hood L. Molecular cloning of translocations involving chromosome 15 and the immunoglobulin C alpha gene from chromosome 12 in two murine plasmacytomas. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6994–6998. doi: 10.1073/pnas.79.22.6994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Calos M. P., Miller J. H. Transposable elements. Cell. 1980 Jul;20(3):579–595. doi: 10.1016/0092-8674(80)90305-0. [DOI] [PubMed] [Google Scholar]
  6. Cohen J. B., Unger T., Rechavi G., Canaani E., Givol D. Rearrangement of the oncogene c-mos in mouse myeloma NSI and hybridomas. Nature. 1983 Dec 22;306(5945):797–799. doi: 10.1038/306797a0. [DOI] [PubMed] [Google Scholar]
  7. Crews S., Barth R., Hood L., Prehn J., Calame K. Mouse c-myc oncogene is located on chromosome 15 and translocated to chromosome 12 in plasmacytomas. Science. 1982 Dec 24;218(4579):1319–1321. doi: 10.1126/science.7146913. [DOI] [PubMed] [Google Scholar]
  8. Davidson W. F., Pierce J. H., Rudikoff S., Morse H. C., 3rd Relationships between B cell and myeloid differentiation. Studies with a B lymphocyte progenitor line, HAFTL-1. J Exp Med. 1988 Jul 1;168(1):389–407. doi: 10.1084/jem.168.1.389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. DePinho R. A., Legouy E., Feldman L. B., Kohl N. E., Yancopoulos G. D., Alt F. W. Structure and expression of the murine N-myc gene. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1827–1831. doi: 10.1073/pnas.83.6.1827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Distel R. J., Ro H. S., Rosen B. S., Groves D. L., Spiegelman B. M. Nucleoprotein complexes that regulate gene expression in adipocyte differentiation: direct participation of c-fos. Cell. 1987 Jun 19;49(6):835–844. doi: 10.1016/0092-8674(87)90621-0. [DOI] [PubMed] [Google Scholar]
  11. Farabaugh P. J., Fink G. R. Insertion of the eukaryotic transposable element Ty1 creates a 5-base pair duplication. Nature. 1980 Jul 24;286(5771):352–356. doi: 10.1038/286352a0. [DOI] [PubMed] [Google Scholar]
  12. Franza B. R., Jr, Rauscher F. J., 3rd, Josephs S. F., Curran T. The Fos complex and Fos-related antigens recognize sequence elements that contain AP-1 binding sites. Science. 1988 Mar 4;239(4844):1150–1153. doi: 10.1126/science.2964084. [DOI] [PubMed] [Google Scholar]
  13. Frischauf A. M., Lehrach H., Poustka A., Murray N. Lambda replacement vectors carrying polylinker sequences. J Mol Biol. 1983 Nov 15;170(4):827–842. doi: 10.1016/s0022-2836(83)80190-9. [DOI] [PubMed] [Google Scholar]
  14. Golay J., Introna M., Graf T. A single point mutation in the v-ets oncogene affects both erythroid and myelomonocytic cell differentiation. Cell. 1988 Dec 23;55(6):1147–1158. doi: 10.1016/0092-8674(88)90259-0. [DOI] [PubMed] [Google Scholar]
  15. Gonda T. J., Cory S., Sobieszczuk P., Holtzman D., Adams J. M. Generation of altered transcripts by retroviral insertion within the c-myb gene in two murine monocytic leukemias. J Virol. 1987 Sep;61(9):2754–2763. doi: 10.1128/jvi.61.9.2754-2763.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gubler U., Hoffman B. J. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. doi: 10.1016/0378-1119(83)90230-5. [DOI] [PubMed] [Google Scholar]
  17. Hanahan D. Studies on transformation of Escherichia coli with plasmids. J Mol Biol. 1983 Jun 5;166(4):557–580. doi: 10.1016/s0022-2836(83)80284-8. [DOI] [PubMed] [Google Scholar]
  18. Higuchi Y., Setoguchi M., Yoshida S., Akizuki S., Yamamoto S. Enhancement of c-fos expression is associated with activated macrophages. Oncogene. 1988 May;2(5):515–521. [PubMed] [Google Scholar]
  19. Holmes K. L., Pierce J. H., Davidson W. F., Morse H. C., 3rd Murine hematopoietic cells with pre-B or pre-B/myeloid characteristics are generated by in vitro transformation with retroviruses containing fes, ras, abl, and src oncogenes. J Exp Med. 1986 Aug 1;164(2):443–457. doi: 10.1084/jem.164.2.443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jaenisch R. Endogenous retroviruses. Cell. 1983 Jan;32(1):5–6. doi: 10.1016/0092-8674(83)90491-9. [DOI] [PubMed] [Google Scholar]
  21. Katoh K., Sawai S., Ueno K., Kondoh H. Complete nucleotide sequence and exon-intron boundaries of the 5' non-coding region of the mouse N-myc gene. Nucleic Acids Res. 1988 Apr 25;16(8):3589–3589. doi: 10.1093/nar/16.8.3589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Katzir N., Rechavi G., Cohen J. B., Unger T., Simoni F., Segal S., Cohen D., Givol D. "Retroposon" insertion into the cellular oncogene c-myc in canine transmissible venereal tumor. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1054–1058. doi: 10.1073/pnas.82.4.1054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Klinken S. P., Alexander W. S., Adams J. M. Hemopoietic lineage switch: v-raf oncogene converts Emu-myc transgenic B cells into macrophages. Cell. 1988 Jun 17;53(6):857–867. doi: 10.1016/s0092-8674(88)90309-1. [DOI] [PubMed] [Google Scholar]
  24. Kohl N. E., Kanda N., Schreck R. R., Bruns G., Latt S. A., Gilbert F., Alt F. W. Transposition and amplification of oncogene-related sequences in human neuroblastomas. Cell. 1983 Dec;35(2 Pt 1):359–367. doi: 10.1016/0092-8674(83)90169-1. [DOI] [PubMed] [Google Scholar]
  25. Kohl N. E., Legouy E., DePinho R. A., Nisen P. D., Smith R. K., Gee C. E., Alt F. W. Human N-myc is closely related in organization and nucleotide sequence to c-myc. Nature. 1986 Jan 2;319(6048):73–77. doi: 10.1038/319073a0. [DOI] [PubMed] [Google Scholar]
  26. Kozak C. A. Retroviruses as chromosomal genes in the mouse. Adv Cancer Res. 1985;44:295–336. doi: 10.1016/s0065-230x(08)60030-5. [DOI] [PubMed] [Google Scholar]
  27. Landschulz W. H., Johnson P. F., McKnight S. L. The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins. Science. 1988 Jun 24;240(4860):1759–1764. doi: 10.1126/science.3289117. [DOI] [PubMed] [Google Scholar]
  28. Majors J. E., Varmus H. E. Nucleotide sequences at host-proviral junctions for mouse mammary tumour virus. Nature. 1981 Jan 22;289(5795):253–258. doi: 10.1038/289253a0. [DOI] [PubMed] [Google Scholar]
  29. Morse B., Rotherg P. G., South V. J., Spandorfer J. M., Astrin S. M. Insertional mutagenesis of the myc locus by a LINE-1 sequence in a human breast carcinoma. Nature. 1988 May 5;333(6168):87–90. doi: 10.1038/333087a0. [DOI] [PubMed] [Google Scholar]
  30. Nilsen T. W., Maroney P. A., Goodwin R. G., Rottman F. M., Crittenden L. B., Raines M. A., Kung H. J. c-erbB activation in ALV-induced erythroblastosis: novel RNA processing and promoter insertion result in expression of an amino-truncated EGF receptor. Cell. 1985 Jul;41(3):719–726. doi: 10.1016/s0092-8674(85)80052-0. [DOI] [PubMed] [Google Scholar]
  31. Perlmutter R. M., Klotz J. L., Pravtcheva D., Ruddle F., Hood L. A novel 6:10 chromosomal translocation in the murine plasmacytoma NS-1. Nature. 1984 Feb 2;307(5950):473–476. doi: 10.1038/307473a0. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Poiesz B. J., Ruscetti F. W., Gazdar A. F., Bunn P. A., Minna J. D., Gallo R. C. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7415–7419. doi: 10.1073/pnas.77.12.7415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Rechavi G., Givol D., Canaani E. Activation of a cellular oncogene by DNA rearrangement: possible involvement of an IS-like element. Nature. 1982 Dec 16;300(5893):607–611. doi: 10.1038/300607a0. [DOI] [PubMed] [Google Scholar]
  35. Schnieke A., Stuhlmann H., Harbers K., Chumakov I., Jaenisch R. Endogenous Moloney leukemia virus in nonviremic Mov substrains of mice carries defects in the proviral genome. J Virol. 1983 Feb;45(2):505–513. doi: 10.1128/jvi.45.2.505-513.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Schwab M., Alitalo K., Klempnauer K. H., Varmus H. E., Bishop J. M., Gilbert F., Brodeur G., Goldstein M., Trent J. Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour. Nature. 1983 Sep 15;305(5931):245–248. doi: 10.1038/305245a0. [DOI] [PubMed] [Google Scholar]
  37. Schwab M., Varmus H. E., Bishop J. M. Human N-myc gene contributes to neoplastic transformation of mammalian cells in culture. Nature. 1985 Jul 11;316(6024):160–162. doi: 10.1038/316160a0. [DOI] [PubMed] [Google Scholar]
  38. Seeger R. C., Brodeur G. M., Sather H., Dalton A., Siegel S. E., Wong K. Y., Hammond D. Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. N Engl J Med. 1985 Oct 31;313(18):1111–1116. doi: 10.1056/NEJM198510313131802. [DOI] [PubMed] [Google Scholar]
  39. Selten G., Cuypers H. T., Boelens W., Robanus-Maandag E., Verbeek J., Domen J., van Beveren C., Berns A. The primary structure of the putative oncogene pim-1 shows extensive homology with protein kinases. Cell. 1986 Aug 15;46(4):603–611. doi: 10.1016/0092-8674(86)90886-x. [DOI] [PubMed] [Google Scholar]
  40. Setoguchi M., Yoshida S., Higuchi Y., Akizuki S., Yamamoto S. Molecular analysis of expression of parental cell properties in hybrids between monocytes and a myeloma cell line. Somat Cell Mol Genet. 1988 Sep;14(5):427–438. doi: 10.1007/BF01534710. [DOI] [PubMed] [Google Scholar]
  41. Shen-Ong G. L., Morse H. C., 3rd, Potter M., Mushinski J. F. Two modes of c-myb activation in virus-induced mouse myeloid tumors. Mol Cell Biol. 1986 Feb;6(2):380–392. doi: 10.1128/mcb.6.2.380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Shen-Ong G. L., Potter M., Mushinski J. F., Lavu S., Reddy E. P. Activation of the c-myb locus by viral insertional mutagenesis in plasmacytoid lymphosarcomas. Science. 1984 Nov 30;226(4678):1077–1080. doi: 10.1126/science.6093260. [DOI] [PubMed] [Google Scholar]
  43. Shimotohno K., Mizutani S., Temin H. M. Sequence of retrovirus provirus resembles that of bacterial transposable elements. Nature. 1980 Jun 19;285(5766):550–554. doi: 10.1038/285550a0. [DOI] [PubMed] [Google Scholar]
  44. Shinnick T. M., Lerner R. A., Sutcliffe J. G. Nucleotide sequence of Moloney murine leukaemia virus. Nature. 1981 Oct 15;293(5833):543–548. doi: 10.1038/293543a0. [DOI] [PubMed] [Google Scholar]
  45. Slamon D. J., Boone T. C., Seeger R. C., Keith D. E., Chazin V., Lee H. C., Souza L. M. Identification and characterization of the protein encoded by the human N-myc oncogene. Science. 1986 May 9;232(4751):768–772. doi: 10.1126/science.3008339. [DOI] [PubMed] [Google Scholar]
  46. Stanton L. W., Schwab M., Bishop J. M. Nucleotide sequence of the human N-myc gene. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1772–1776. doi: 10.1073/pnas.83.6.1772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Stong R. C., Korsmeyer S. J., Parkin J. L., Arthur D. C., Kersey J. H. Human acute leukemia cell line with the t(4;11) chromosomal rearrangement exhibits B lineage and monocytic characteristics. Blood. 1985 Jan;65(1):21–31. [PubMed] [Google Scholar]
  48. Taya Y., Mizusawa S., Nishimura S. Nucleotide sequence of the coding region of the mouse N-myc gene. EMBO J. 1986 Jun;5(6):1215–1219. doi: 10.1002/j.1460-2075.1986.tb04349.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Van Beveren C., Rands E., Chattopadhyay S. K., Lowy D. R., Verma I. M. Long terminal repeat of murine retroviral DNAs: sequence analysis, host-proviral junctions, and preintegration site. J Virol. 1982 Feb;41(2):542–556. doi: 10.1128/jvi.41.2.542-556.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Weinstein Y., Cleveland J. L., Askew D. S., Rapp U. R., Ihle J. N. Insertion and truncation of c-myb by murine leukemia virus in a myeloid cell line derived from cultures of normal hematopoietic cells. J Virol. 1987 Jul;61(7):2339–2343. doi: 10.1128/jvi.61.7.2339-2343.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Yancopoulos G. D., Nisen P. D., Tesfaye A., Kohl N. E., Goldfarb M. P., Alt F. W. N-myc can cooperate with ras to transform normal cells in culture. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5455–5459. doi: 10.1073/pnas.82.16.5455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Zimmerman K. A., Yancopoulos G. D., Collum R. G., Smith R. K., Kohl N. E., Denis K. A., Nau M. M., Witte O. N., Toran-Allerand D., Gee C. E. Differential expression of myc family genes during murine development. 1986 Feb 27-Mar 5Nature. 319(6056):780–783. doi: 10.1038/319780a0. [DOI] [PubMed] [Google Scholar]
  53. van Lohuizen M., Breuer M., Berns A. N-myc is frequently activated by proviral insertion in MuLV-induced T cell lymphomas. EMBO J. 1989 Jan;8(1):133–136. doi: 10.1002/j.1460-2075.1989.tb03357.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. van Lohuizen M., Verbeek S., Krimpenfort P., Domen J., Saris C., Radaszkiewicz T., Berns A. Predisposition to lymphomagenesis in pim-1 transgenic mice: cooperation with c-myc and N-myc in murine leukemia virus-induced tumors. Cell. 1989 Feb 24;56(4):673–682. doi: 10.1016/0092-8674(89)90589-8. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES