Long-distance activation of the Myc protooncogene by provirus insertion in Mlvi-1 or Mlvi-4 in rat T-cell lymphomas (original) (raw)

Abstract

T-cell lymphomas induced by Moloney murine leukemia virus frequently have proviruses integrated at the Mlvi-4 and Mlvi-1 loci, which map approximately 30 and 270 kilobases 3' of the promoter region of the Myc protooncogene, respectively. Provirus insertion in these loci is responsible for the activation of adjacent genes. To determine whether Myc expression was also affected by these provirus insertions, we constructed T-cell hybrids between two rat thymic lymphomas containing a provirus in Mlvi-4 or Mlvi-1 and the murine T-cell lymphoma line BW5147. These hybrids segregated the provirus-containing rearranged alleles from the normal nonrearranged alleles of Mlvi-4 and Mlvi-1, and they carried an intact copy of rat Myc. Using an S1 nuclease protection assay, we observed that the expression of the rat Myc cosegregated with the rearranged Mlvi-4 or Mlvi-1 locus. However, provirus insertion in these loci had no effect on promoter utilization or on the expression of the murine Myc locus. We conclude that provirus insertion exerts a long-range cis effect on the expression of Myc. Therefore, provirus integration in a single locus may affect the expression of multiple genes, some of which may be located a long distance from the site of integration.

170

Images in this article

Selected References

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

  1. Bear S. E., Bellacosa A., Lazo P. A., Jenkins N. A., Copeland N. G., Hanson C., Levan G., Tsichlis P. N. Provirus insertion in Tpl-1, an Ets-1-related oncogene, is associated with tumor progression in Moloney murine leukemia virus-induced rat thymic lymphomas. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7495–7499. doi: 10.1073/pnas.86.19.7495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berger S. L. Isolation of cytoplasmic RNA: ribonucleoside-vanadyl complexes. Methods Enzymol. 1987;152:227–234. doi: 10.1016/0076-6879(87)52024-9. [DOI] [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. Cesarman E., Dalla-Favera R., Bentley D., Groudine M. Mutations in the first exon are associated with altered transcription of c-myc in Burkitt lymphoma. Science. 1987 Nov 27;238(4831):1272–1275. doi: 10.1126/science.3685977. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Cory S., Graham M., Webb E., Corcoran L., Adams J. M. Variant (6;15) translocations in murine plasmacytomas involve a chromosome 15 locus at least 72 kb from the c-myc oncogene. EMBO J. 1985 Mar;4(3):675–681. doi: 10.1002/j.1460-2075.1985.tb03682.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Croce C. M., Thierfelder W., Erikson J., Nishikura K., Finan J., Lenoir G. M., Nowell P. C. Transcriptional activation of an unrearranged and untranslocated c-myc oncogene by translocation of a C lambda locus in Burkitt. Proc Natl Acad Sci U S A. 1983 Nov;80(22):6922–6926. doi: 10.1073/pnas.80.22.6922. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dzierzak E. A., Papayannopoulou T., Mulligan R. C. Lineage-specific expression of a human beta-globin gene in murine bone marrow transplant recipients reconstituted with retrovirus-transduced stem cells. Nature. 1988 Jan 7;331(6151):35–41. doi: 10.1038/331035a0. [DOI] [PubMed] [Google Scholar]
  9. Erikson J., Nishikura K., ar-Rushdi A., Finan J., Emanuel B., Lenoir G., Nowell P. C., Croce C. M. Translocation of an immunoglobulin kappa locus to a region 3' of an unrearranged c-myc oncogene enhances c-myc transcription. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7581–7585. doi: 10.1073/pnas.80.24.7581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Finver S. N., Nishikura K., Finger L. R., Haluska F. G., Finan J., Nowell P. C., Croce C. M. Sequence analysis of the MYC oncogene involved in the t(8;14)(q24;q11) chromosome translocation in a human leukemia T-cell line indicates that putative regulatory regions are not altered. Proc Natl Acad Sci U S A. 1988 May;85(9):3052–3056. doi: 10.1073/pnas.85.9.3052. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Forrester W. C., Takegawa S., Papayannopoulou T., Stamatoyannopoulos G., Groudine M. Evidence for a locus activation region: the formation of developmentally stable hypersensitive sites in globin-expressing hybrids. Nucleic Acids Res. 1987 Dec 23;15(24):10159–10177. doi: 10.1093/nar/15.24.10159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Forrester W. C., Thompson C., Elder J. T., Groudine M. A developmentally stable chromatin structure in the human beta-globin gene cluster. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1359–1363. doi: 10.1073/pnas.83.5.1359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gefter M. L., Margulies D. H., Scharff M. D. A simple method for polyethylene glycol-promoted hybridization of mouse myeloma cells. Somatic Cell Genet. 1977 Mar;3(2):231–236. doi: 10.1007/BF01551818. [DOI] [PubMed] [Google Scholar]
  14. Graham M., Adams J. M., Cory S. Murine T lymphomas with retroviral inserts in the chromosomal 15 locus for plasmacytoma variant translocations. 1985 Apr 25-May 1Nature. 314(6013):740–743. doi: 10.1038/314740a0. [DOI] [PubMed] [Google Scholar]
  15. Grosveld F., van Assendelft G. B., Greaves D. R., Kollias G. Position-independent, high-level expression of the human beta-globin gene in transgenic mice. Cell. 1987 Dec 24;51(6):975–985. doi: 10.1016/0092-8674(87)90584-8. [DOI] [PubMed] [Google Scholar]
  16. Henglein B., Synovzik H., Groitl P., Bornkamm G. W., Hartl P., Lipp M. Three breakpoints of variant t(2;8) translocations in Burkitt's lymphoma cells fall within a region 140 kilobases distal from c-myc. Mol Cell Biol. 1989 May;9(5):2105–2113. doi: 10.1128/mcb.9.5.2105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jacobson A. Purification and fractionation of poly(A)+ RNA. Methods Enzymol. 1987;152:254–261. doi: 10.1016/0076-6879(87)52028-6. [DOI] [PubMed] [Google Scholar]
  18. Jarman A. P., Higgs D. R. Nuclear scaffold attachment sites in the human globin gene complexes. EMBO J. 1988 Nov;7(11):3337–3344. doi: 10.1002/j.1460-2075.1988.tb03205.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Koehne C. F., Lazo P. A., Alves K., Lee J. S., Tsichlis P. N., O'Donnell P. V. The Mlvi-1 locus involved in the induction of rat T-cell lymphomas and the pvt-1/Mis-1 locus are identical. J Virol. 1989 May;63(5):2366–2369. doi: 10.1128/jvi.63.5.2366-2369.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kozak C. A., Strauss P. G., Tsichlis P. N. Genetic mapping of a cellular DNA region involved in induction of thymic lymphomas (Mlvi-1) to mouse chromosome 15. Mol Cell Biol. 1985 Apr;5(4):894–897. doi: 10.1128/mcb.5.4.894. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lazo P. A., Tsichlis P. N. Recombination between two integrated proviruses, one of which was inserted near c-myc in a retrovirus-induced rat thymoma: implications for tumor progression. J Virol. 1988 Mar;62(3):788–794. doi: 10.1128/jvi.62.3.788-794.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lemay G., Jolicoeur P. Rearrangement of a DNA sequence homologous to a cell-virus junction fragment in several Moloney murine leukemia virus-induced rat thymomas. Proc Natl Acad Sci U S A. 1984 Jan;81(1):38–42. doi: 10.1073/pnas.81.1.38. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Loc P. V., Strätling W. H. The matrix attachment regions of the chicken lysozyme gene co-map with the boundaries of the chromatin domain. EMBO J. 1988 Mar;7(3):655–664. doi: 10.1002/j.1460-2075.1988.tb02860.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mengle-Gaw L., Rabbitts T. H. A human chromosome 8 region with abnormalities in B cell, HTLV-I+ T cell and c-myc amplified tumours. EMBO J. 1987 Jul;6(7):1959–1965. doi: 10.1002/j.1460-2075.1987.tb02458.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Morse B., South V. J., Rothberg P. G., Astrin S. M. Somatic mutation and transcriptional deregulation of myc in endemic Burkitt's lymphoma disease: heptamer-nonamer recognition mistakes? Mol Cell Biol. 1989 Jan;9(1):74–82. doi: 10.1128/mcb.9.1.74. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Neil J. C., Forrest D. Mechanisms of retrovirus-induced leukaemia: selected aspects. Biochim Biophys Acta. 1987 Apr 20;907(1):71–91. doi: 10.1016/0304-419x(87)90019-9. [DOI] [PubMed] [Google Scholar]
  28. Nishikura K., Murray J. M. The mechanism of inactivation of the normal c-myc gene locus in human Burkitt lymphoma cells. Oncogene. 1988 May;2(5):493–498. [PubMed] [Google Scholar]
  29. Nishikura K., ar-Rushdi A., Erikson J., Watt R., Rovera G., Croce C. M. Differential expression of the normal and of the translocated human c-myc oncogenes in B cells. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4822–4826. doi: 10.1073/pnas.80.15.4822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rabbitts T. H., Forster A., Hamlyn P., Baer R. Effect of somatic mutation within translocated c-myc genes in Burkitt's lymphoma. Nature. 1984 Jun 14;309(5969):592–597. doi: 10.1038/309592a0. [DOI] [PubMed] [Google Scholar]
  31. Selten G., Cuypers H. T., Berns A. Proviral activation of the putative oncogene Pim-1 in MuLV induced T-cell lymphomas. EMBO J. 1985 Jul;4(7):1793–1798. doi: 10.1002/j.1460-2075.1985.tb03852.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Selten G., Cuypers H. T., Zijlstra M., Melief C., Berns A. Involvement of c-myc in MuLV-induced T cell lymphomas in mice: frequency and mechanisms of activation. EMBO J. 1984 Dec 20;3(13):3215–3222. doi: 10.1002/j.1460-2075.1984.tb02281.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Steffen D. Proviruses are adjacent to c-myc in some murine leukemia virus-induced lymphomas. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2097–2101. doi: 10.1073/pnas.81.7.2097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Tsichlis P. N., Lohse M. A., Szpirer C., Szpirer J., Levan G. Cellular DNA regions involved in the induction of rat thymic lymphomas (Mlvi-1, Mlvi-2, Mlvi-3, and c-myc) represent independent loci as determined by their chromosomal map location in the rat. J Virol. 1985 Dec;56(3):938–942. doi: 10.1128/jvi.56.3.938-942.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Tsichlis P. N. Oncogenesis by Moloney murine leukemia virus. Anticancer Res. 1987 Mar-Apr;7(2):171–180. [PubMed] [Google Scholar]
  37. Tsichlis P. N., Shepherd B. M., Bear S. E. Activation of the Mlvi-1/mis1/pvt-1 locus in Moloney murine leukemia virus-induced T-cell lymphomas. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5487–5491. doi: 10.1073/pnas.86.14.5487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Tsichlis P. N., Strauss P. G., Hu L. F. A common region for proviral DNA integration in MoMuLV-induced rat thymic lymphomas. 1983 Mar 31-Apr 6Nature. 302(5907):445–449. doi: 10.1038/302445a0. [DOI] [PubMed] [Google Scholar]
  39. Tsichlis P. N., Strauss P. G., Lohse M. A. Concerted DNA rearrangements in Moloney murine leukemia virus-induced thymomas: a potential synergistic relationship in oncogenesis. J Virol. 1985 Oct;56(1):258–267. doi: 10.1128/jvi.56.1.258-267.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Varmus H. E. The molecular genetics of cellular oncogenes. Annu Rev Genet. 1984;18:553–612. doi: 10.1146/annurev.ge.18.120184.003005. [DOI] [PubMed] [Google Scholar]
  41. Varmus H. Retroviruses. Science. 1988 Jun 10;240(4858):1427–1435. doi: 10.1126/science.3287617. [DOI] [PubMed] [Google Scholar]
  42. Vijaya S., Steffen D. L., Kozak C., Robinson H. L. Dsi-1, a region with frequent proviral insertions in Moloney murine leukemia virus-induced rat thymomas. J Virol. 1987 Apr;61(4):1164–1170. doi: 10.1128/jvi.61.4.1164-1170.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Villemur R., Monczak Y., Rassart E., Kozak C., Jolicoeur P. Identification of a new common provirus integration site in gross passage A murine leukemia virus-induced mouse thymoma DNA. Mol Cell Biol. 1987 Jan;7(1):512–522. doi: 10.1128/mcb.7.1.512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Villeneuve L., Rassart E., Jolicoeur P., Graham M., Adams J. M. Proviral integration site Mis-1 in rat thymomas corresponds to the pvt-1 translocation breakpoint in murine plasmacytomas. Mol Cell Biol. 1986 May;6(5):1834–1837. doi: 10.1128/mcb.6.5.1834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Wang X. F., Calame K. The endogenous immunoglobulin heavy chain enhancer can activate tandem VH promoters separated by a large distance. Cell. 1985 Dec;43(3 Pt 2):659–665. doi: 10.1016/0092-8674(85)90238-7. [DOI] [PubMed] [Google Scholar]