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British Journal of Cancer logoLink to British Journal of Cancer
. 1978 Feb;37(2):139–158. doi: 10.1038/bjc.1978.23

RNA-tumour-virus genes and transforming genes: patterns of transmission.

G J Todaro
PMCID: PMC2009600  PMID: 204320

Abstract

RNA tumour virus genes are contained in the chromosomal DNA of most vertebrates, and may be transmitted vertically from parent to progeny along with other cellular genes, as well as horizontally as infectious particles. Activation of these viral genes may be part of the means by which RNA tumour viruses produce cancer. Viral genes and their possible gene products have been characterized. The envelope glycoprotein, for example, interacts with specific membrane receptors on cell surfaces and the major phosphoprotein binds to specific viral RNA sequences. Type-C viral gene sequences have evolved as the species have evolved, and have been transferred between distantly related species under natural conditions. The presence of genetically transmitted viral genes in several vertebrate species, including primates, and the evidence that they may provide normal functions beneficial to the species carrying them, suggests that the potential to cause cancer is a pathological manifestation of a normal physiological process.

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Selected References

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  1. Aaronson S. A., Stephenson J. R. Endogenous type-C RNA viruses of mammalian cells. Biochim Biophys Acta. 1976 Dec 23;458(4):323–354. doi: 10.1016/0304-419x(76)90006-8. [DOI] [PubMed] [Google Scholar]
  2. Aaronson S. A., Todaro G. J. Basis for the acquisition of malignant potential by mouse cells cultivated in vitro. Science. 1968 Nov 29;162(3857):1024–1026. doi: 10.1126/science.162.3857.1024. [DOI] [PubMed] [Google Scholar]
  3. Armelin H. A. Pituitary extracts and steroid hormones in the control of 3T3 cell growth. Proc Natl Acad Sci U S A. 1973 Sep;70(9):2702–2706. doi: 10.1073/pnas.70.9.2702. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baltimore D. Tumor viruses: 1974. Cold Spring Harb Symp Quant Biol. 1975;39(Pt 2):1187–1200. doi: 10.1101/sqb.1974.039.01.137. [DOI] [PubMed] [Google Scholar]
  5. Benveniste R. E., Callahan R., Sherr C. J., Chapman V., Todaro G. J. Two distinct endogenous type C viruses isolated from the asian rodent Mus cervicolor: conservation of virogene sequences in related rodent species. J Virol. 1977 Mar;21(3):849–862. doi: 10.1128/jvi.21.3.849-862.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Benveniste R. E., Sherr C. J., Todaro G. J. Evolution of type C viral genes: origin of feline leukemia virus. Science. 1975 Nov 28;190(4217):886–888. doi: 10.1126/science.52892. [DOI] [PubMed] [Google Scholar]
  7. Benveniste R. E., Todaro G. J. Evolution of primate oncornaviruses: An endogenous virus from langurs (Presbytis spp.) with related virogene sequences in other Old World monkeys. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4557–4561. doi: 10.1073/pnas.74.10.4557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Benveniste R. E., Todaro G. J. Evolution of type C viral genes: I. Nucleic acid from baboon type C virus as a measure of divergence among primate species. Proc Natl Acad Sci U S A. 1974 Nov;71(11):4513–4518. doi: 10.1073/pnas.71.11.4513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Benveniste R. E., Todaro G. J. Evolution of type C viral genes: evidence for an Asian origin of man. Nature. 1976 May 13;261(5556):101–108. doi: 10.1038/261101a0. [DOI] [PubMed] [Google Scholar]
  10. Benveniste R. E., Todaro G. J. Evolution of type C viral genes: preservation of ancestral murine type C viral sequences in pig cellular DNA. Proc Natl Acad Sci U S A. 1975 Oct;72(10):4090–4094. doi: 10.1073/pnas.72.10.4090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Benveniste R. E., Todaro G. J. Homology between type-C viruses of various species as determined by molecular hybridization. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3316–3320. doi: 10.1073/pnas.70.12.3316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Benveniste R. E., Todaro G. J. Multiple divergent copies of endogenous C-type virogenes in mammalian cells. Nature. 1974 Nov 8;252(5479):170–173. doi: 10.1038/252170a0. [DOI] [PubMed] [Google Scholar]
  13. COHEN S. Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal. J Biol Chem. 1962 May;237:1555–1562. [PubMed] [Google Scholar]
  14. Callahan R., Benveniste R. E., Sherr C. J., Schidlovsky G., Todaro G. J. A new class of genetically transmitted retravirus isolated from Mus cervicolor. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3579–3583. doi: 10.1073/pnas.73.10.3579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Carpenter G., Cohen S. Human epidermal growth factor and the proliferation of human fibroblasts. J Cell Physiol. 1976 Jun;88(2):227–237. doi: 10.1002/jcp.1040880212. [DOI] [PubMed] [Google Scholar]
  16. Cohen S., Carpenter G., Lembach K. J. Interaction of epidermal growth factor (EGF) with cultured fibroblasts. Adv Metab Disord. 1975;8:265–284. doi: 10.1016/b978-0-12-027308-9.50024-x. [DOI] [PubMed] [Google Scholar]
  17. Cohen S., Taylor J. M. Epidermal growth factor: chemical and biological characterization. Recent Prog Horm Res. 1974;30(0):533–550. doi: 10.1016/b978-0-12-571130-2.50017-1. [DOI] [PubMed] [Google Scholar]
  18. Colcher D., Heberling R. L., Kalter S. S., Schlom J. Squirrel monkey retrovirus: an endogenous virus of a new world primate. J Virol. 1977 Aug;23(2):294–301. doi: 10.1128/jvi.23.2.294-301.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Duff R., Rapp F. Quantitative assay for transformation of 3T3 cells by herpes simplex virus type 2. J Virol. 1975 Mar;15(3):490–496. doi: 10.1128/jvi.15.3.490-496.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Dulak N. C., Temin H. M. A partially purified polypeptide fraction from rat liver cell conditioned medium with multiplication-stimulating activity for embryo fibroblasts. J Cell Physiol. 1973 Apr;81(2):153–160. doi: 10.1002/jcp.1040810204. [DOI] [PubMed] [Google Scholar]
  21. Eisenman R., Vogt V. M., Diggelmann H. Synthesis of avian RNA tumor virus structural proteins. Cold Spring Harb Symp Quant Biol. 1975;39(Pt 2):1067–1075. doi: 10.1101/sqb.1974.039.01.122. [DOI] [PubMed] [Google Scholar]
  22. Essex M., Cotter S. M., Carpenter J. L., Hardy W. D., Jr, Hess P., Jarrett W., Schaller J., Yohn D. S. Feline oncornavirus-associated cell membrane antigen. II. Antibody titers in healthy cats from household and laboratory colony environments. J Natl Cancer Inst. 1975 Mar;54(3):631–635. [PubMed] [Google Scholar]
  23. Essex M., Klein G., Snyder S. P., Harrold J. B. Antibody to feline oncornavirus-associated cell membrane antigen in neonatal cats. Int J Cancer. 1971 Nov 15;8(3):384–390. doi: 10.1002/ijc.2910080305. [DOI] [PubMed] [Google Scholar]
  24. Essex M., Klein G., Snyder S. P., Harrold J. B. Correlation between humoral antibody and regression of tumours induced by feline sarcoma virus. Nature. 1971 Sep 17;233(5316):195–196. doi: 10.1038/233195a0. [DOI] [PubMed] [Google Scholar]
  25. Essex M., Sliski A., Cotter S. M., Jakowski R. R., Hardy W. D., Jr Immunosurveillance of naturally occurring feline leukemia. Science. 1975 Nov 21;190(4216):790–792. doi: 10.1126/science.173019. [DOI] [PubMed] [Google Scholar]
  26. Essex M., Sliski A., Hardy W. D., Jr, Cotter S. M. Immune response to leukemia virus and tumor-associated antigens in cats. Cancer Res. 1976 Feb;36(2 Pt 2):640–645. [PubMed] [Google Scholar]
  27. Fabricant R. N., De Larco J. E., Todaro G. J. Nerve growth factor receptors on human melanoma cells in culture. Proc Natl Acad Sci U S A. 1977 Feb;74(2):565–569. doi: 10.1073/pnas.74.2.565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Fischinger P. J., Peebles P. T., Nomura S., Haapala D. K. Isolation of RD-114-like oncornavirus from a cat cell line. J Virol. 1973 Jun;11(6):978–985. doi: 10.1128/jvi.11.6.978-985.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Frankel A. E., Fischinger P. J. Rate of divergence of cellular sequences homologous to segments of Moloney sarcoma virus. J Virol. 1977 Jan;21(1):153–160. doi: 10.1128/jvi.21.1.153-160.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Giard D. J., Aaronson S. A., Todaro G. J., Arnstein P., Kersey J. H., Dosik H., Parks W. P. In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors. J Natl Cancer Inst. 1973 Nov;51(5):1417–1423. doi: 10.1093/jnci/51.5.1417. [DOI] [PubMed] [Google Scholar]
  31. Hardy W. D., Jr, Old L. J., Hess P. W., Essex M., Cotter S. Horizontal transmission of feline leukaemia virus. Nature. 1973 Aug 3;244(5414):266–269. doi: 10.1038/244266a0. [DOI] [PubMed] [Google Scholar]
  32. Heberling R. L., Barker S. T., Kalter S. S., Smith G. C., Helmke R. J. Oncornavirus: isolation from a squirrel monkey (Saimiri sciureus) lung culture. Science. 1977 Jan 21;195(4275):289–292. doi: 10.1126/science.63993. [DOI] [PubMed] [Google Scholar]
  33. Hellström I., Hellström K. E. Some recent studies on cellular immunity to human melanomas. Fed Proc. 1973 Feb;32(2):156–159. [PubMed] [Google Scholar]
  34. Henderson I. C., Lieber M. M., Todaro G. J. Mink cell line Mv 1 Lu (CCL 64). Focus formation and the generation of "nonproducer" transformed cell lines with murine and feline sarcoma viruses. Virology. 1974 Jul;60(1):282–287. doi: 10.1016/0042-6822(74)90386-9. [DOI] [PubMed] [Google Scholar]
  35. Hollenberg M. D., Cuatrecasas P. Insulin and epidermal growth factor. Human fibroblast receptors related to deoxyribonucleic acid synthesis and amino acid uptake. J Biol Chem. 1975 May 25;250(10):3845–3853. [PubMed] [Google Scholar]
  36. Huebner R. J., Todaro G. J. Oncogenes of RNA tumor viruses as determinants of cancer. Proc Natl Acad Sci U S A. 1969 Nov;64(3):1087–1094. doi: 10.1073/pnas.64.3.1087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Kawakami T. G., Buckley P. M. Antigenic studies on gibbon type-C viruses. Transplant Proc. 1974 Jun;6(2):193–196. [PubMed] [Google Scholar]
  38. Kawakami T. G., Huff S. D., Buckley P. M., Dungworth D. L., Synder S. P., Gilden R. V. C-type virus associated with gibbon lymphosarcoma. Nat New Biol. 1972 Feb 9;235(58):170–171. doi: 10.1038/newbio235170a0. [DOI] [PubMed] [Google Scholar]
  39. Lerner R. A., Wilson C. B., Villano B. C., McConahey P. J., Dixon F. J. Endogenous oncornaviral gene expression in adult and fetal mice: quantitative, histologic, and physiologic studies of the major viral glycorprotein, gp70. J Exp Med. 1976 Jan 1;143(1):151–166. doi: 10.1084/jem.143.1.151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Levi-Montalcini R., Angeletti P. U. Nerve growth factor. Physiol Rev. 1968 Jul;48(3):534–569. doi: 10.1152/physrev.1968.48.3.534. [DOI] [PubMed] [Google Scholar]
  41. Lieber M. M., Livingston D. M., Todaro G. J. Superinduction of endogenous type C virus by 5-bromodeoxyuridine from transformed mouse clones. Science. 1973 Aug 3;181(4098):443–444. doi: 10.1126/science.181.4098.443. [DOI] [PubMed] [Google Scholar]
  42. Lieber M. M., Sherr C. J., Todaro G. J., Benveniste R. E., Callahan R., Coon H. G. Isolation from the asian mouse Mus caroli of an endogenous type C virus related to infectious primate type C viruses. Proc Natl Acad Sci U S A. 1975 Jun;72(6):2315–2319. doi: 10.1073/pnas.72.6.2315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Livingston D. M., Todaro G. J. Endogenous type C virus from a cat cell clone with properties distinct from previously described feline type C virus. Virology. 1973 May;53(1):142–151. doi: 10.1016/0042-6822(73)90473-x. [DOI] [PubMed] [Google Scholar]
  44. Olson C., Miller L. D., Miller J. M., Hoss H. E. Transmission of lymphosarcoma from cattle to sheep. J Natl Cancer Inst. 1972 Nov;49(5):1463–1467. [PubMed] [Google Scholar]
  45. Pollock E. J., Aaronson S. A., Todaro G. J. X-irradiation of Balb-3T3. Sarcoma-forming ability and virus induction. Int J Radiat Biol Relat Stud Phys Chem Med. 1970;17(1):97–100. doi: 10.1080/09553007014550111. [DOI] [PubMed] [Google Scholar]
  46. Revoltella R., Bertolini L., Pediconi M., Vigneti E. Specific binding of nerve growth factor (NGF) by murine C 1300 neuroblastoma cells. J Exp Med. 1974 Aug 1;140(2):437–451. doi: 10.1084/jem.140.2.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Rice N. R., Straus N. A. Relatedness of mouse satellite deoxyribonucleic acid to deoxyribonucleic acid of various Mus species. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3546–3550. doi: 10.1073/pnas.70.12.3546. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Scolnick E. M., Maryak J. M., Parks W. P. Levels of rat cellular RNA homologous to either Kirsten sarcoma virus or rat type-C virus in cell lines derived from Osborne-Mendel rats. J Virol. 1974 Dec;14(6):1435–1444. doi: 10.1128/jvi.14.6.1435-1444.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Sen A., Sherr C. J., Todaro G. J. Specific binding of the type C viral core protein p12 with purified viral RNA. Cell. 1976 Jan;7(1):21–32. doi: 10.1016/0092-8674(76)90251-8. [DOI] [PubMed] [Google Scholar]
  50. Sen A., Todaro G. J. The genome-associated, specific RNA binding proteins of avian and mammalian type C viruses. Cell. 1977 Jan;10(1):91–99. doi: 10.1016/0092-8674(77)90143-x. [DOI] [PubMed] [Google Scholar]
  51. Sherr C. J., Benveniste R. E., Lieber M. M., Todaro G. J. Type C viruses from Kirsten sarcoma-transformed mink cells co-cultivated with primate cells and expressing p30 antigens related to feline leukemia virus. J Virol. 1976 Aug;19(2):346–358. doi: 10.1128/jvi.19.2.346-358.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Sherr C. J., Benveniste R. E., Todaro G. J. Type C viral expression in primate tissues. Proc Natl Acad Sci U S A. 1974 Sep;71(9):3721–3725. doi: 10.1073/pnas.71.9.3721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Shoyab M., Baluda M. A. Homology between avian oncornavirus RNAs and DNA from several avian species. J Virol. 1975 Dec;16(6):1492–1502. doi: 10.1128/jvi.16.6.1492-1502.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Sliski A. H., Essex M., Meyer C., Todaro G. Feline oncornavirus-associated cell membrane antigen: expression in transformed nonproducer mink cells. Science. 1977 Jun 17;196(4296):1336–1339. doi: 10.1126/science.194310. [DOI] [PubMed] [Google Scholar]
  55. Stehelin D., Guntaka R. V., Varmus H. E., Bishop J. M. Purification of DNA complementary to nucleotide sequences required for neoplastic transformation of fibroblasts by avian sarcoma viruses. J Mol Biol. 1976 Mar 5;101(3):349–365. doi: 10.1016/0022-2836(76)90152-2. [DOI] [PubMed] [Google Scholar]
  56. TODARO G. J., GREEN H. Quantitative studies of the growth of mouse embryo cells in culture and their development into established lines. J Cell Biol. 1963 May;17:299–313. doi: 10.1083/jcb.17.2.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Todaro G. J., Benveniste R. E., Callahan R., Lieber M. M., Sherr C. J. Endogenous primate and feline type C viruses. Cold Spring Harb Symp Quant Biol. 1975;39(Pt 2):1159–1168. doi: 10.1101/sqb.1974.039.01.133. [DOI] [PubMed] [Google Scholar]
  58. Todaro G. J., Benveniste R. E., Sherr C. J., Schlom J., Schidlovsky G., Stephenson J. R. Isolation and characterization of a new type D retrovirus from the asian primate, Presbytis obscurus (spectacled langur). Virology. 1978 Jan;84(1):189–194. doi: 10.1016/0042-6822(78)90231-3. [DOI] [PubMed] [Google Scholar]
  59. Todaro G. J., De Larco J. E., Cohen S. Transformation by murine and feline sarcoma viruses specifically blocks binding of epidermal growth factor to cells. Nature. 1976 Nov 4;264(5581):26–31. doi: 10.1038/264026a0. [DOI] [PubMed] [Google Scholar]
  60. Todaro G. J., De Larco J. E., Nissley S. P., Rechler M. M. MSA and EGF receptors on sarcoma virus transformed cells and human fibrosarcoma cells in culture. Nature. 1977 Jun 9;267(5611):526–528. doi: 10.1038/267526a0. [DOI] [PubMed] [Google Scholar]
  61. Todaro G. J., Habel K., Green H. Antigenic and cultural properties of cells doubly transformed by polyoma virus and SV40. Virology. 1965 Oct;27(2):179–185. doi: 10.1016/0042-6822(65)90157-1. [DOI] [PubMed] [Google Scholar]
  62. Todaro G. J., Lieber M. M., Benveniste R. E., Sherr C. J. Infectious primate type C viruses: Three isolates belonging to a new subgroup from the brains of normal gibbons. Virology. 1975 Oct;67(2):335–343. doi: 10.1016/0042-6822(75)90435-3. [DOI] [PubMed] [Google Scholar]
  63. Todaro G. J., Sherr C. J., Benveniste R. E. Baboons and their close relatives are unusual among primates in their ability to release nondefective endogenous type C viruses. Virology. 1976 Jul 1;72(1):278–282. doi: 10.1016/0042-6822(76)90331-7. [DOI] [PubMed] [Google Scholar]
  64. Todaro G. J., Sherr C. J., Benveniste R. E., Lieber M. M., Melnick J. L. Type C viruses of baboons: isolation from normal cell cultures. Cell. 1974 May;2(1):55–61. doi: 10.1016/0092-8674(74)90008-7. [DOI] [PubMed] [Google Scholar]
  65. Todaro G. J., Tevethia S. S., Melnick J. L. Isolation of an RD-114 related type-C virus from feline sarcoma virus-transformed baboon cells. Intervirology. 1973;1(5):399–404. doi: 10.1159/000148868. [DOI] [PubMed] [Google Scholar]
  66. Vogt V. M., Eisenman R., Diggelmann H. Generation of avian myeloblastosis virus structural proteins by proteolytic cleavage of a precursor polypeptide. J Mol Biol. 1975 Aug 15;96(3):471–493. doi: 10.1016/0022-2836(75)90174-6. [DOI] [PubMed] [Google Scholar]
  67. Westermark B. Density dependent proliferation of human glia cells stimulated by epidermal growth factor. Biochem Biophys Res Commun. 1976 Mar 22;69(2):304–310. doi: 10.1016/0006-291x(76)90522-2. [DOI] [PubMed] [Google Scholar]
  68. Wolfe L. G., Deinhardt F., Theilen G. H., Rabin H., Kawakami T., Bustad L. K. Induction of tumors in marmoset monkeys by simian sarcoma virus, type 1 (Lagothrix): a preliminary report. J Natl Cancer Inst. 1971 Nov;47(5):1115–1120. [PubMed] [Google Scholar]

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