Skip to main content

The Oncogene and its Potential Role in Carcinogenesis

  • Conference paper
Receptors and Other Targets for Toxic Substances

Part of the book series: Archives of Toxicology ((TOXICOLOGY,volume 8))

Abstract

Cellular onc genes are a group of evolutionarily conserved sequences which are homologous to the transforming genes (v-onc) of oncogenic retroviruses. Although their functions in normal cells are largely not known, the sequence homology between viral and cellular onc genes is consistent with the idea that neoplastic transformation may, in some cases, be due to abnormal levels of cellular onc gene expression. Several models can be proposed for such a mechanism, including the insertion nearby of a viral promoter, alteration of the physiological promoter by a mutagenic agent, gene amplification, relocation in a transcriptionally active region of the genome as a consequence of chromosomal rearrangements and point mutations induced by external factors. Examples of these different mechanisms of onc gene activation can be found in animal and human tumors. Finally, the detail description of one cellular one gene (c-sis), its relation to the viral gene and to a known cellular growth factor and its possible mode of activation in neoplastic transformation is presented.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Bishop, J.M. (1978) Retroviruses. Ann Rvw Biochem 47, 35–88.

    Article  CAS  Google Scholar 

  • Bishop, J.M. (1983) Cellular oncogenes and retroviruses. Ann Rvw Biochem 52, 301–354.

    Article  CAS  Google Scholar 

  • Blick, M., Westin, E., Gutterman, J., Wong-Staal, F., Gallo, R., McCredie, K., Keating, M., and Murphy, E. (1984) Oncogene expression in human leukemia. Blood, 64, 1234–1239.

    PubMed  CAS  Google Scholar 

  • Clarke, M.F., Westin, E., Schmidt, D., Josephs, S.F., Ratner, L., Wong-Staal, F., Gallo, R.C., and Reitz, M.S., Jr. (1984) Transformation of NIH3T3 cells by a human c-sis cDNA clone. Nature 308, 464–467.

    Article  PubMed  CAS  Google Scholar 

  • Collins, S., and Groudine, M. (1982) Amplification of endogenous myc-related DNA sequences in a human myeloid leukemia cell line. Nature 298, 679–681.

    Article  PubMed  CAS  Google Scholar 

  • Dalla Favera, R., Gelmann, E.P., Gallo, R.C., and Wong-Staal, F. (1981) A human one gene homologous to the transforming gene (v-sis) of simian sarcoma virus. Nature 292, 31–35.

    Article  Google Scholar 

  • Dalla Favera, R., Bregni, M., Erikson, J., Patterson, D., Gallo, R.C., and Croce, C.M. (1982a) Human cmyc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma. Proc Nat USA 79, 7824–7827.

    Article  Google Scholar 

  • Dalla Favera, R., Wong-Staal, F., and Gallo, R.C. (1982b) Onc gene amplification in promyelocytic leukemia cell line HL-60 and primary leukemia cells of the same patient. Nature 299, 61–63.

    Article  Google Scholar 

  • Deuel, T.F., Huang, J.S., Proffitt, R.T., Baenziger, J.U., Chang, D., and Kennedy, B.B. (1982) Human platelet derived growth factor. Purification and resolution into two active protein fractions. J Biol Chem 256, 8896–8899.

    Google Scholar 

  • Devare, S.G., Reddy, E.P., Law, J.D., Robbins, K.C., and Aaronson, S.A. (1983) Nucleotide sequence of the simian sarcoma virus genome: demonstration that its acquired cellular sequences encode the transforming gene product p28 sis. Proc Nat Acad Sci USA 80, 731–735.

    Article  PubMed  CAS  Google Scholar 

  • Doolittle, R.F., Hunkapiller, M.W., Hood, L.E., Devare, S.G., Robbins, K.C., Aaronson, S.A., and Antoniades, H.N. (1983) Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science 221, 275–277.

    Article  PubMed  CAS  Google Scholar 

  • Downward, J., Yarden, Y., Mayes, E., Scrace, G., Totty, N., Stockwell, P., Ullrich, A., Schlessinger, J., and Waterfield, M.D. (1984) Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature 307, 521–527.

    Article  PubMed  CAS  Google Scholar 

  • Eva, A., Robbins, K.C., Andersen, P.R., Srinivasan, A., Tronick, S.R., Reddy, E.P., Ellmore, N.W., Galen, A.T., Lautenberger, J.A., Papas, T.S., Westin, E.H., Wong-Staal, F., Gallo, R.C., and Aaronson, S.A. (1982) Cellular genes analogous to retroviral onc genes are transcribed in human tumor cells. Nature 295, 116–119.

    Article  PubMed  CAS  Google Scholar 

  • Gallo, R.C., and Wong-Staal, F. (1982) Retroviruses and etiological agents of some human and animal leukemias and lymphomas and as tools to elucidate the molecular mechanism of leukemogenesis. Blood 60, 545–557.

    PubMed  CAS  Google Scholar 

  • Gelmann, E.P., Wong-Staal, F., Kramer, R.A., and Gallo, R.C. (1981) Molecular cloning and comparative analyses of the genomes of simian sarcoma virus and its associated helper virus. Proc Nat Acad Sci USA 78, 3373–3377.

    Article  PubMed  CAS  Google Scholar 

  • Guroff, G. (1983) Growth and Maturation Factors, vol. 1, John Wiley & Sons, New York.

    Google Scholar 

  • Hayward, W.S., Neel, B.G., and Astrin, S.M. (1981) Activation of a cellular onc gene by promoter insertion in ALV-induced lymphoid leukosis. Nature 290, 375–480.

    Article  Google Scholar 

  • Josephs, S.F., Guo, C., Ratner, L., and Wong-Staal, F. (1984) Human proto-oncogene nucleotide sequences corresponding to the transforming region of simian sarcoma virus. Science 223, 487–491.

    Article  PubMed  CAS  Google Scholar 

  • Josephs, S.F., Ratner, L., Clarke, M.F., Westin, E.H., Reitz, M.S., and Wong-Staal, F. (1984) Transforming potential of the normal human c-sis nucleotide sequences encoding a chain of platelet derived growth factor. Science, 225, 636–639.

    Article  PubMed  CAS  Google Scholar 

  • Kelly, K., Cochran, B.H., Stiles, C.D., and Leder, P. (1983) Cell-specific regulation of the c-myc gee by lymphocyte mitogens and platelet-derived growth factor. Cell 35, 603–610.

    Article  PubMed  CAS  Google Scholar 

  • Klein, G. (1983) Specific chromosomal translocations and the genesis of B-cell-derived tumors in mice and men. Cell 32, 311–315.

    Article  PubMed  CAS  Google Scholar 

  • Land, H., Parada, L.F., and Weinberg, R.A. (1983) Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature 304, 596–602.

    Article  PubMed  CAS  Google Scholar 

  • Marcu, K.B., Harris, L.J., Stanton, L.W., Erikson, J., Watt, R., and Croce, C.M. (1983) Transcriptionally active c-myc oncogene is contained within NIARD, a DNA sequence associated with chromosome translocations in B-cell neoplasia. Proc Nat Acad Sci USA 80, 519–523.

    Article  PubMed  CAS  Google Scholar 

  • Nusse, R., and Varmus, H.E. (1982) Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell 31, 99–109.

    Article  PubMed  CAS  Google Scholar 

  • Santos, E., Tronick, S.R., Aaronson, S.A., Pulciani, S., and Barbacid, M. (1982) T24 human bladder carcinoma oncogene is an activated form of the normal human homologue of Balb and Harvey MS transforming genes. Nature 298, 343–347.

    Article  PubMed  CAS  Google Scholar 

  • Stiles, C.D. (1983) The molecular biology of platelet-derived growth factor. Cell 33, 653–655.

    Article  PubMed  CAS  Google Scholar 

  • Tabin, C.J., Bradley, S.M., Bargmann, C.I., Weinberg, R.A., Papageorge, A.G., Scolnick, E.M., Dhar, R., Lowy, D.R., and Chang, E.H. (1982) Mechanism of activation of a human oncogene. Nature 300, 143–149.

    Article  PubMed  CAS  Google Scholar 

  • Taparowsky, E., Suard, Y., Fasano, O., Shimizu, K., Goldfarb, M., and Wigler, M. (1982) Activation of the T24 bladder carcinoma transforming gene is linked to a single amino acid change. Nature 300, 762–765.

    Article  PubMed  CAS  Google Scholar 

  • Theilen, G.H., Gould, D., Fowler, M., and Dungworth, D.L. (1971) C-type virus in tumor tissue of a woolly monkey ( Lagothrix spp.) with fibrosarcoma. J Natl Cancer Inst 47, 881–889.

    PubMed  CAS  Google Scholar 

  • Tsichlis, P.N., Strauss, P.G., and Hu, L.F. (1983) A common region for proviral DNA integration in MoMuLV-induced rat thymic lymphomas. Nature 302, 445–447.

    Article  PubMed  CAS  Google Scholar 

  • Waterfield, M.D., Scrace, T., Whittle, N., Stroobant, P., Johnsson, A., Wasteson, A., Westermark, B., Heldin, C.-H., Huang, J.S., and Deuel, T.F. (1983) Platelet-derived growth factor is structurally related to the putative transforming protein p28 sis of simian sarcoma virus. Nature 304, 35–39.

    Article  PubMed  CAS  Google Scholar 

  • Westin, E.H., Gallo, R.C., Arya, S.K., Eva, A., Souza, L.M., Baluda, M.A., Aaronson, S.A., and Wong-Staal, F. (1982a) Differential expression of the AMV gene in human hematopoietic cells. Proc Nat Acad Sci USA 79, 2194–2198.

    Article  PubMed  CAS  Google Scholar 

  • 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., and Gallo, R.C. (1982b) Expression of cellular homologues of retroviral one genes in human hematopoietic cells. Proc Nat Acad Sci USA 79, 2490–2494.

    Article  PubMed  CAS  Google Scholar 

  • Wolfe, L.G., Deinhardt, F., Theilen, G.H., Rabin, H., Kawakami, T., and Bustad, L.K. (1971) Induction of tumors in marmoset monkeys by simian sarcoma virus, type 1 (Lagothrix): a preliminary report. J Natl Cancer Inst 47, 1115–1120.

    PubMed  CAS  Google Scholar 

  • Wong-Staal, F., Dalla-Favera, R., Franchini, G., Gelmann, E.P., and Gallo, R.C. (1981a) Three distinct genes in human DNA related to the transforming genes of mammalian sarcoma retroviruses. Science 213, 226–228.

    Article  PubMed  CAS  Google Scholar 

  • Wong-Staal, F., Dalla-Favera, R., Gelmann, E.P., Manzari, V., Szala, S., Josephs, S.F., and Gallo, R.C. (1981b) The v-sis transforming gene of simian sarcoma virus is a new one gene of primate origin. Nature 294, 273–275.

    Article  Google Scholar 

  • Wong-Staal, F., and Gallo, R.C. (1982) The transforming genes of primate and other retroviruses and their human homologues. In Advances in Viral Oncology. Klein, G. (ed). Vol I. Raven Press, New York, pp 153–171.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1985 Springer-Verlag

About this paper

Cite this paper

Wong-Staal, F. (1985). The Oncogene and its Potential Role in Carcinogenesis. In: Chambers, P.L., Cholnoky, E., Chambers, C.M. (eds) Receptors and Other Targets for Toxic Substances. Archives of Toxicology, vol 8. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-69928-3_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-69928-3_6

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-13670-5

  • Online ISBN: 978-3-642-69928-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics