c-Myb in Smooth Muscle Cells

  • Michael Simons
  • Robert D. Rosenberg
Part of the Methods in Molecular Medicine book series (MIMM, volume 1)


The proto-oncogene c-myb is a cellular homolog of a viral oncogene v-myb found in two independently derived avian acute leukemia viruses: avian myeloblastosis vn-us (AMV) and E26 leukemia virus (1). The myb gene is highly conserved in eukaryotes, and it usually consists of 15 exons spanning over 35 kb of genomic DNA (1).In humans, c-myb gene locus has been mapped to chromosome 6 (6q22-23) However, myb mRNA expressed in thymus contains transcripts originating from chromosome 17 (17q25), suggesting that an mtermolecular recombinant event may be involved in the formation of the mature protein (2).


Smooth Muscle Cell Vascular Smooth Muscle Cell Antisense Oligonucleotide Smooth Muscle Cell Proliferation Neointimal Formation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Shen-Ong, G. L C (1990) The myb oncogene. Biochem Biophys Acta 1032, 39–52.PubMedGoogle Scholar
  2. 2.
    Vellard, M., Soret, J., VIegas-Pequlgnot, E., Galibert, F, Cong, N. V, Dutnllaux, B., and Perbal, B (1991) c-Myb protooncogene evidence for mtermolecular recombmation of coding sequences Oncogene 6, 505–514.PubMedGoogle Scholar
  3. 3.
    Dudek, H. and Reddy, E P (1989) Identification of two translational products for c-myb. Oncogene 4, 1061–1066PubMedGoogle Scholar
  4. 4.
    Frampton, J., Gibson, T J., Ness, S. A., Doderlein, G., and Graf, T. (1991) Proposed structure for the DNA-binding domain of the c-myb oncoprotem based on model building and mutational analysis. Prot Eng 4, 891–901CrossRefGoogle Scholar
  5. 5.
    Gabnelsen, O S., Sentenac, A, and Fromageot, P. (1991) Specific DNA binding by c-Myb′ evidence for a double helix-turn-helix-related motif Science 253, 1140–1143.CrossRefGoogle Scholar
  6. 6.
    Howe, K M., Reakes, C F., and Watson, R J (1990) Characterlzation of the sequence-specific mteraction of mouse c-myb protem with DNA, EMBO J 9, 161–169.PubMedGoogle Scholar
  7. 7.
    Nishma, Y., Nakagoshl, H., Imamoto, F., Gonda, T. J., and Ishil, S (1989) Trans-activation by the c-myb proto-oncogene Nucleic Acid Res 17, 107–117CrossRefGoogle Scholar
  8. 8.
    Dudek, H., Tantravahl, R. V., Rao, V. N., Reddy, E. S., and Reddy, E. P (1992) Myb and Ets proteins cooperate in transcriptional activation of the mim-1 promoter Proc Natl Acad Sci USA 89, 1291–1295PubMedCrossRefGoogle Scholar
  9. 9.
    Evans, J. L., Moore, T L., Kuehl, W. M., Bender, T., and Ting, J. P. (1990) Functional analysis of c-Myb protein in T-lymphocytlc cell lines shows that It trans-activates the c-myc promoter Mol. Cell Biol. 10, 5747–5752.PubMedGoogle Scholar
  10. 10.
    Ramsay, R. G., Ishii, S., and Gonda, T. J. (1992) Interaction of the myb protein with specific DNA binding sites. J. Biol Chem. 267, 5656–5662PubMedGoogle Scholar
  11. 11.
    Thompson, C B., Challoner, P. B., Neiman, P E., and Groudme, M (1986) Expression of the c-myb proto-oncogene during cellular prohferation. Nature 319, 374–380.PubMedCrossRefGoogle Scholar
  12. 12.
    Griffin, C A and Baylm, S B (1985) Expression of the c-myb oncogene in human small cell lung carcmoma Cancer Res 45, 272–275PubMedGoogle Scholar
  13. 13.
    Melam, C., Rivoltini, L., Parnuam, G., Calabretta, B., and Colombo, M P (1991) Inhibition of proliferation by c-myb antisense ohgodeoxynucleotides in colon adenocarcmoma cell lines that express c-myb Cancer Res 51, 2897–2901.Google Scholar
  14. 14.
    Raschella, G., Negrom, A, Skorski, T, Pucci, S., Nieborowska-Skorska, M., Romeo, A., and Calabretta, B (1992) Inhibition of proliferation by c-myb antisense RNA and oligodeoxynucleotrdes in transformed neuroectodermal cell lines. Cancer Res 52, 4221–4226PubMedGoogle Scholar
  15. 15.
    Dyson, P J., Poirier, F., and Watson, R. J (1989) Expression of c-myb in embryo-nal carcinoma cells and embryonal stem cells. Differentiation 42, 24–27PubMedCrossRefGoogle Scholar
  16. 16.
    Brown, K E., Kmdy, M S., and Sonenshein, G E (1992) Expression of the c-myb proto-oncogene in bovine vascular smooth muscle cells J Biol Chem 267, 4625–4630.PubMedGoogle Scholar
  17. 17.
    Luscher, B. and Eisenman, R N (1990) New light on Myc and Myb Part II Myb Genes Dev 4, 2235–2241.PubMedCrossRefGoogle Scholar
  18. 18.
    Clarke, M F., Kukowska-Latallo, J F., Westm, E., Smith, M., and Prochowmk, E. V. (1988) Constnutive expression of a c-myb cDNA blocks Friend murine erythroleukemia cell differentiation Mol Cell Biol 8, 884–892PubMedGoogle Scholar
  19. 19.
    Travah, S., Ferber, A., Reiss, K., Sell, C., Koniecki, J., Calabretta, B., and Baserga, R (1991) Effect of the myb gene product on expression of the PCNA gene in fibroblasts Oncogene 6, 887–894.Google Scholar
  20. 20.
    Simons, M. and Rosenberg, R D (1992) Antisense nonmuscle myosin heavy chain and c-myb oligonucleotides suppress smooth muscle cell proliferation in vitro. Cwc Res 70, 835–843Google Scholar
  21. 21.
    Anfossl, G., Gewutz, A M., and Calabretta, B. (1989) An obgomer complemen-tary to c-myb-encoded mRNA inhibits proliferation of human myeloid leukemia cell lines. Proc Natl. Acad Sci USA 86, 3379–3383CrossRefGoogle Scholar
  22. 22.
    Lipsick, J. S. and Boyle, W. J. (1987) c-myb protein expression is a late event during T-lymphocyte activation Mol Cell Biol 7, 3358–3360PubMedGoogle Scholar
  23. 23.
    Sm, G., Wurster, A L., Lipstck, J. S., and Hedrick, S M.(1992) Expression of the CD4 gene requires a Myb transcription factor. Mol Cell Biol 12, 1592–1604.Google Scholar
  24. 24.
    Gewu-tz, A. M. and Calabretta, B. (1991) Role of the c-myb and c-abl protooncogenes in human hematopotesis. Ann NY Acad Sci 62, 63–73.Google Scholar
  25. 25.
    Weston, K. M (1990) The myb genes Semen Cancer Biol 1, 371–382.Google Scholar
  26. 26.
    Reilly, C F., Kmdy, M. S., Brown, K. E., Rosenberg, R. D., and Sonenshem, G E (1989) Heparm prevents vascular smooth muscle cell progression through the G1 phase of the cell cycle. J Biol Chem 264, 6990–6995PubMedGoogle Scholar
  27. 27.
    Simons, M., Morgan, K. G., Parker, C., Collm, E., and Rosenberg, R D. (1993) Proto-oncogene c-myb mediates an mtracellular calcium rise during the late G1 phase of the cell cycle J Biol Chem 268, 621–632.Google Scholar
  28. 28.
    Keith, C H., Ratan, R., Maxfield, F R., BaJer, A., and Shelanski, Z. (1985) Local cytoplasmic calcium gradients in hving mitotic cells. Nature 316, 848–850.PubMedCrossRefGoogle Scholar
  29. 29.
    Poeme, M., Alderton, J., Steinhardt, R, and Tsien, R (1986) Calcium rises abruptly and briefly throughout the cell at the onset of anaphase. Science 233, 886–889CrossRefGoogle Scholar
  30. 30.
    Steinhardt, R A. and Alderton, J. (1988) Intracellular free calcium rtse trtggers nuclear envelope breakdown in the sea urchin embryo Nature 332, 364–366PubMedCrossRefGoogle Scholar
  31. 31.
    Twigg, J., Patel, R., and Whitaker, M. (1988) Translational control of InsP3-Induced chromatm condensatron during the early cycles of sea urchin embryos. Nature 332, 366–369PubMedCrossRefGoogle Scholar
  32. 32.
    Sisken, J E., Silver, R B., Barrows, G H., and Grasch, S. D (1985) Studies on the role of Ca++ ions in cell division wtth the use of fluorescent probes and quan-titative video intensification mtcroscopy, in Advances in Microscopy (_Cowden, R R. and Harrtson, F W., eds.), Liss, New York, pp 73–87Google Scholar
  33. 33.
    McIntosh, J. R and Koonce, M. P. (1989) Mttosts. Science 246, 622–628.PubMedCrossRefGoogle Scholar
  34. 34.
    Paul, D. and Ristom, H J. J (1979) Cell cycle control by Ca++ ions in mouse 3T3 cells and in transformed 3T3 cells J Cell Physiol. 98, 3l–40CrossRefGoogle Scholar
  35. 35.
    Pardee, A. B., Dubrow, R., Hamlin, J. L., and Kletzien, R. F. (1978) Animal cell cycle Ann. Rev Blochem 47, 715–750CrossRefGoogle Scholar
  36. 36.
    Stmons, M., Hideao, A., Salzman, E. W., and Rosenberg, R D. (1995) c-Myb affects intracellular calcium handling in vascular smooth muscle cells Am J. Physiol. Cell Physiol 37, C856–C868Google Scholar
  37. 37.
    Garratt, K N., Edwards, W D., Kaufmann, U P., Vliestra, R E., and Holmes, D R., Jr (1991) Differential histopathology of primary atherosclerotic and restenottc lessons in coronary arterres and saphenous vein bypass grafts: analysts of tissue obtained from 73 patients by directional atherectomy. J Am Coll Cardiol 17, 442–448PubMedCrossRefGoogle Scholar
  38. 38.
    Dilley, R J., Mcgeachte, J. K., and Prendergast, F J (1988) A review of the histological changes in vein-to-artery grafts, with particular reference to mttmal hyperplana. Arch Surg 123, 691–696PubMedGoogle Scholar
  39. 39.
    Schwartz, S. M and Retdy, M A. (1987) Common, mechamsms of prolifera-tion of smooth muscle in atherosclerosis and hypertension Human Pathol 18, 240–247CrossRefGoogle Scholar
  40. 40.
    Schwartz, S. M, Campbell, G. R., and Campbell, J. H. (1986) Replication of smooth muscle cells in vascular disease. Circ. Res 58, 427–444.PubMedGoogle Scholar
  41. 41.
    Kocher, O., Gabbiani, F., Gabbiam, G., Retdy, M A., Cokay, M. S., Peters, H., and Huttner, I (1991) Phenotypic features of smooth muscle cells during the evolution of experimental carotid artery intimal thickening Lab Invest 65, 459–470PubMedGoogle Scholar
  42. 42.
    Ross, R (1986) The pathogenesis of atherosclerosts an update. N Engl J Med 314, 488–500.PubMedCrossRefGoogle Scholar
  43. 43.
    Clowes, A. W., Clowes, M M., Fingerle, J., and Retdy, M A. (1989) Kinetics of cellular proliferation after arterial iqury. V. Role of acute distension in the mduc-tron of smooth muscle proliferation Lab Invest 60, 360–364PubMedGoogle Scholar
  44. 44.
    Clowes, A. W., Retdy, M A, and Clowes, M. M. (1983) Kinetics of cellular proliferation after arterial qury I. Smooth muscle growth in the absence of endothelium. Lab Invest 49, 327–333PubMedGoogle Scholar
  45. 45.
    Fingerle, J., Johnson, R., Clowes, A W, MaJesky, M. W., and Retdy, M. A. (1989) Role of platelets in smooth muscle cell proliferation and migration after vascular injury in rat carotid artery Proc Natl Acad Sci USA 86, 8412–8416PubMedCrossRefGoogle Scholar
  46. 46.
    Gewutz, A M., Anfossi, G., Venturelli, D., Valpreda, S., Sims, R., and Calabretta, B. (1989) G1/S transition in normal human T-lymphocytes requires the nuclear protein encoded by c-myb Science 245, 180–183CrossRefGoogle Scholar
  47. 47.
    Reilly, C. F (1990) Rat vascular smooth muscle cells mnnortahzed with SV40 large T antigen possess defined smooth muscle cell characteristics including growth inhibition by heparin J Cell Physiol. 142, 342–351PubMedCrossRefGoogle Scholar
  48. 48.
    Gales, R V. and Todd, D M (1992) Increased spectfictty for antisense olrgodeoxy-nucleotide targeting of RNA cleavage by RNase H using chimeric methylphos-phonodiester/phosphodrester structures, Nucleic Acid Res 20, 763–770.CrossRefGoogle Scholar
  49. 49.
    Woolf, T M., Jennings, C G., Rebagliatt, M., and Melton, D A (1990) The stability, toxicrty and effectiveness of unmodified and phosphorothioate antisense ohgodeoxynucleotides in Xenopus oocytes and embryos Nucleic Acid Res. 18, 1763–1769.PubMedCrossRefGoogle Scholar
  50. 50.
    Woolf, T M., Melton, D A., and Jennings, C G (1992) Spectficity of antisense ohgonucleottdes in vivo Proc Natl Acad Sci USA 89, 7305–7309PubMedCrossRefGoogle Scholar
  51. 51.
    Block, L C., Griffin, L C, Latham, J A., Vermass, E. H.,and Toole, J. J (1992) Selection of single-stranded DNA molecules that bind and inhabit human thrombin Nature 355, 564–566CrossRefGoogle Scholar
  52. 52.
    Guvakova, M A., Yakubov, L A, Vlodavsky, I, Tonkinson, J L, and Stein, C A (1995) Phosphothtoate oligodeoxynucleotides bind to basic Iibroblast growth fac-tor, mhibit its binding to cell-surface receptors, and remove tt from low affinity binding sites on extracellular matrix J Biol. Chem 270, 2620–2627.PubMedCrossRefGoogle Scholar
  53. 53.
    Offerman, M. K. and Medford, R. M (1993) Induction of VCAM-1 gene expres-sion by double-stranded RNA occurs by a p68 kmase-dependent pathway in endothelial cells. Clin Res 41, 262a (abstr)Google Scholar
  54. 54.
    Edelman, E. R., Nugent, M A., Smith, L T., and Karnovsky, M J. (1992) Basic fibroblast growth factor enhances the coupling of intimal hyperplasta and proliferation of vasa vasorum in injured rat artertes J Clin Invest 89, 465–473PubMedCrossRefGoogle Scholar
  55. 55.
    Simons, M., Edelman, E R., DeKeyser, J. L., Langer, R., and Rosenberg, R D. (1992) Antisense c-myb oligonucleotides inhibit intimal arterial smooth muscle cell accumulation in vivo Nature 359, 67–70.PubMedCrossRefGoogle Scholar
  56. 56.
    Guyton, J. R., Rosenberg, R D., Clowes, A W., and Karnovsky, M J. (1980) Inhibition of rat arterial smooth muscle cell proltferation by heparm In vtvo stud-ies with anticoagulant and nonanticoagulant heparin. Circ. Res 46, 625–634PubMedGoogle Scholar
  57. 57.
    Agrawal, S., Temsamam, J., and Tang, J. Y (1991) Pharmacokmetms, biodistribution, and stabtlrty of ohgodeoxynucleottde phosphorothloates in mice. Proc Natl Acad. Sci USA 88 7595–7599.PubMedCrossRefGoogle Scholar
  58. 58.
    Temsamani, J., Tang, J. Y., and Agrawal, S. (1992) Capped oligodeoxynucleotide phosphorothioates Pharmacokinetics and stability in mice Ann NY Acad Sci 660, 318–320PubMedCrossRefGoogle Scholar
  59. 59.
    Goodarzr, G., Watabe, M., and Watabe, K (1992) Organ distribution and stability of phosphorothioated oligodeoxyrtbonucleotides in mice Biopharm. Drug Dispos 13, 22l–227.Google Scholar
  60. 60.
    Bennett, M. R., Anglm, S., McEwan, J R., Jagoe R., Newby, A. C., and Evan, G. I. (1994) Inhibition of vascular smooth muscle cell proliferation in vitro and in vivo by c-myc antisense oligodeoxynucleotides J Clin Invest. 93, 820–828PubMedCrossRefGoogle Scholar
  61. 61.
    Simons, M., Edelman, E R., and Rosenberg, R. D. (1994) Antisense PCNA oli-gonucleotides Inhibit intimal hyperplasia in a rat carotid injury model. J Clin Invest 93, 235l–2356CrossRefGoogle Scholar
  62. 62.
    Abe, J., Zhou, W., Taguchi, J., Takuwa, N., Miki, K., Okazaki, H., Kurokawa, K., Kumada, M., and Takuwa, Y (1994) Suppression of neointimal smooth muscle cell accumulation in vivo by antisense cdc2 and cdk2 oligonucleotides in rat carotid artery Biochem Biophys Res Comm 198, 16–24.PubMedCrossRefGoogle Scholar
  63. 63.
    Edelman, E R., Simons, M, Sirois, M G., and Rosenberg, R. D (1995) c-Myc in vasculoproliferative disese Circ Res 76, 176–182PubMedGoogle Scholar
  64. 64.
    Mortshita, R., Gibbons, G. H., Ellison, K E., Nakajima, M., Zhang, L., Kaneda, Y., Ogihara, T., and Dzau, V. J. (1993) Single intraluminal delivery of antisense cdc2 kinase and proliferating-cell nuclear antigen oligonucleotides results in chronic inhtbition of neointimal hyperplasia. Proc Natl Acad Sci USA 90, 8474–8478CrossRefGoogle Scholar
  65. 65.
    Azrin, M A., Miichel, J F., Pedersen, C., Curley, T., Bow, L M., Alberghint, T V., Waters, D D., and McKay, R. G. (1994) Inhibition of smooth muscle cell proliferation in vivo following local delivery of antisense c-myb oligonucleotides during angioplasty. J Am Coll Cardiol 23, 396A.Google Scholar
  66. 66.
    Shi, Y., Fard, A., Vermain, P., and Zalewski, A (1994) C-Myc antisense oligo-mers reduce neointimal formation in porcine coronary arteries J Am Coll. Cardiol 23, 395AGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 1996

Authors and Affiliations

  • Michael Simons
    • 1
  • Robert D. Rosenberg
    • 1
  1. 1.Department of BiologyMassachusetis Institute of TechnologyCambridge

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