Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1984 Aug;50(2):137–142. doi: 10.1038/bjc.1984.155

The 1984 Walter Hubert lecture. Activation of transforming genes in neoplasms.

G M Cooper
PMCID: PMC1976883  PMID: 6380552

Abstract

Cellular oncogenes have been identified by the biological activity of tumour DNAs in transfection assays and/or by homology to the transforming genes of retroviruses. In some tumours, the biological activity, organization or expression of these genes is altered, suggesting that such alterations contribute to the development of neoplastic disease. Experiments leading to the identification of cellular oncogenes are reviewed and our current understanding of the mechanisms by which they induce transformation of cells in culture and may contribute to the pathogenesis of neoplasms in vivo is discussed.

Full text

PDF
137

Selected References

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

  1. Albino A. P., Le Strange R., Oliff A. I., Furth M. E., Old L. J. Transforming ras genes from human melanoma: a manifestation of tumour heterogeneity? Nature. 1984 Mar 1;308(5954):69–72. doi: 10.1038/308069a0. [DOI] [PubMed] [Google Scholar]
  2. Bister K., Jansen H. W., Graf T., Enrietto P., Hayman M. J. Genome structure of HBI, a variant of acute leukemia virus MC29 with unique oncogenic properties. J Virol. 1983 May;46(2):337–346. doi: 10.1128/jvi.46.2.337-346.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Capon D. J., Seeburg P. H., McGrath J. P., Hayflick J. S., Edman U., Levinson A. D., Goeddel D. V. Activation of Ki-ras2 gene in human colon and lung carcinomas by two different point mutations. Nature. 1983 Aug 11;304(5926):507–513. doi: 10.1038/304507a0. [DOI] [PubMed] [Google Scholar]
  4. Chang E. H., Furth M. E., Scolnick E. M., Lowy D. R. Tumorigenic transformation of mammalian cells induced by a normal human gene homologous to the oncogene of Harvey murine sarcoma virus. Nature. 1982 Jun 10;297(5866):479–483. doi: 10.1038/297479a0. [DOI] [PubMed] [Google Scholar]
  5. Colburn N. H., Talmadge C. B., Gindhart T. D. Transfer of sensitivity to tumor promoters by transfection of DNA from sensitive into insensitive mouse JB6 epidermal cells. Mol Cell Biol. 1983 Jul;3(7):1182–1186. doi: 10.1128/mcb.3.7.1182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cooper G. M., Neiman P. E. Transforming genes of neoplasms induced by avian lymphoid leukosis viruses. Nature. 1980 Oct 16;287(5783):656–659. doi: 10.1038/287656a0. [DOI] [PubMed] [Google Scholar]
  7. Cooper G. M., Neiman P. E. Two distinct candidate transforming genes of lymphoid leukosis virus-induced neoplasms. Nature. 1981 Aug 27;292(5826):857–858. doi: 10.1038/292857a0. [DOI] [PubMed] [Google Scholar]
  8. Cooper G. M., Okenquist S., Silverman L. Transforming activity of DNA of chemically transformed and normal cells. Nature. 1980 Apr 3;284(5755):418–421. doi: 10.1038/284418a0. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Dalla-Favera R., Bregni M., Erikson J., Patterson D., Gallo R. C., Croce C. M. Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7824–7827. doi: 10.1073/pnas.79.24.7824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Der C. J., Cooper G. M. Altered gene products are associated with activation of cellular rasK genes in human lung and colon carcinomas. Cell. 1983 Jan;32(1):201–208. doi: 10.1016/0092-8674(83)90510-x. [DOI] [PubMed] [Google Scholar]
  12. Diamond A., Cooper G. M., Ritz J., Lane M. A. Identification and molecular cloning of the human Blym transforming gene activated in Burkitt's lymphomas. Nature. 1983 Sep 8;305(5930):112–116. doi: 10.1038/305112a0. [DOI] [PubMed] [Google Scholar]
  13. Finkel T., Cooper G. M. Detection of a molecular complex between ras proteins and transferrin receptor. Cell. 1984 Apr;36(4):1115–1121. doi: 10.1016/0092-8674(84)90062-x. [DOI] [PubMed] [Google Scholar]
  14. Finkel T., Der C. J., Cooper G. M. Activation of ras genes in human tumors does not affect localization, modification, or nucleotide binding properties of p21. Cell. 1984 May;37(1):151–158. doi: 10.1016/0092-8674(84)90310-6. [DOI] [PubMed] [Google Scholar]
  15. Furth M. E., Davis L. J., Fleurdelys B., Scolnick E. M. Monoclonal antibodies to the p21 products of the transforming gene of Harvey murine sarcoma virus and of the cellular ras gene family. J Virol. 1982 Jul;43(1):294–304. doi: 10.1128/jvi.43.1.294-304.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gilman A. G. G proteins and dual control of adenylate cyclase. Cell. 1984 Mar;36(3):577–579. doi: 10.1016/0092-8674(84)90336-2. [DOI] [PubMed] [Google Scholar]
  17. Goubin G., Goldman D. S., Luce J., Neiman P. E., Cooper G. M. Molecular cloning and nucleotide sequence of a transforming gene detected by transfection of chicken B-cell lymphoma DNA. Nature. 1983 Mar 10;302(5904):114–119. doi: 10.1038/302114a0. [DOI] [PubMed] [Google Scholar]
  18. Hall A., Marshall C. J., Spurr N. K., Weiss R. A. Identification of transforming gene in two human sarcoma cell lines as a new member of the ras gene family located on chromosome 1. Nature. 1983 Jun 2;303(5916):396–400. doi: 10.1038/303396a0. [DOI] [PubMed] [Google Scholar]
  19. Hayward W. S., Neel B. G., Astrin S. M. Activation of a cellular onc gene by promoter insertion in ALV-induced lymphoid leukosis. Nature. 1981 Apr 9;290(5806):475–480. doi: 10.1038/290475a0. [DOI] [PubMed] [Google Scholar]
  20. Hill M., Hillova J. Virus recovery in chicken cells tested with Rous sarcoma cell DNA. Nat New Biol. 1972 May 10;237(71):35–39. doi: 10.1038/newbio237035a0. [DOI] [PubMed] [Google Scholar]
  21. Krontiris T. G., Cooper G. M. Transforming activity of human tumor DNAs. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1181–1184. doi: 10.1073/pnas.78.2.1181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lane M. A., Neary D., Cooper G. M. Activation of a cellular transforming gene in tumours induced by Abelson murine leukaemia virus. Nature. 1982 Dec 16;300(5893):659–661. doi: 10.1038/300659a0. [DOI] [PubMed] [Google Scholar]
  23. Lane M. A., Sainten A., Cooper G. M. Activation of related transforming genes in mouse and human mammary carcinomas. Proc Natl Acad Sci U S A. 1981 Aug;78(8):5185–5189. doi: 10.1073/pnas.78.8.5185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lane M. A., Sainten A., Cooper G. M. Stage-specific transforming genes of human and mouse B- and T-lymphocyte neoplasms. Cell. 1982 Apr;28(4):873–880. doi: 10.1016/0092-8674(82)90066-6. [DOI] [PubMed] [Google Scholar]
  25. Lane M. A., Sainten A., Doherty K. M., Cooper G. M. Isolation and characterization of a stage-specific transforming gene, Tlym-I, from T-cell lymphomas. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2227–2231. doi: 10.1073/pnas.81.7.2227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Morton C. C., Taub R., Diamond A., Lane M. A., Cooper G. M., Leder P. Mapping of the human Blym-1 transforming gene activated in Burkitt lymphomas to chromosome 1. Science. 1984 Jan 13;223(4632):173–175. doi: 10.1126/science.6691143. [DOI] [PubMed] [Google Scholar]
  27. Nusse R., Varmus H. E. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell. 1982 Nov;31(1):99–109. doi: 10.1016/0092-8674(82)90409-3. [DOI] [PubMed] [Google Scholar]
  28. Parada L. F., Tabin C. J., Shih C., Weinberg R. A. Human EJ bladder carcinoma oncogene is homologue of Harvey sarcoma virus ras gene. Nature. 1982 Jun 10;297(5866):474–478. doi: 10.1038/297474a0. [DOI] [PubMed] [Google Scholar]
  29. Peters G., Brookes S., Smith R., Dickson C. Tumorigenesis by mouse mammary tumor virus: evidence for a common region for provirus integration in mammary tumors. Cell. 1983 Jun;33(2):369–377. doi: 10.1016/0092-8674(83)90418-x. [DOI] [PubMed] [Google Scholar]
  30. Reddy E. P., Reynolds R. K., Santos E., Barbacid M. A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene. Nature. 1982 Nov 11;300(5888):149–152. doi: 10.1038/300149a0. [DOI] [PubMed] [Google Scholar]
  31. Santos E., Tronick S. R., Aaronson S. A., Pulciani S., Barbacid M. T24 human bladder carcinoma oncogene is an activated form of the normal human homologue of BALB- and Harvey-MSV transforming genes. Nature. 1982 Jul 22;298(5872):343–347. doi: 10.1038/298343a0. [DOI] [PubMed] [Google Scholar]
  32. Schäfer R., Griegel S., Dubbert M. A., Willecke K. Unstable transformation of mouse 3T3 cells by transfection with DNA from normal human lymphocytes. EMBO J. 1984 Mar;3(3):659–663. doi: 10.1002/j.1460-2075.1984.tb01863.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Scolnick E. M., Papageorge A. G., Shih T. Y. Guanine nucleotide-binding activity as an assay for src protein of rat-derived murine sarcoma viruses. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5355–5359. doi: 10.1073/pnas.76.10.5355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sefton B. M., Trowbridge I. S., Cooper J. A., Scolnick E. M. The transforming proteins of Rous sarcoma virus, Harvey sarcoma virus and Abelson virus contain tightly bound lipid. Cell. 1982 Dec;31(2 Pt 1):465–474. doi: 10.1016/0092-8674(82)90139-8. [DOI] [PubMed] [Google Scholar]
  35. Shen-Ong G. L., Keath E. J., Piccoli S. P., Cole M. D. Novel myc oncogene RNA from abortive immunoglobulin-gene recombination in mouse plasmacytomas. Cell. 1982 Dec;31(2 Pt 1):443–452. doi: 10.1016/0092-8674(82)90137-4. [DOI] [PubMed] [Google Scholar]
  36. Shih C., Padhy L. C., Murray M., Weinberg R. A. Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts. Nature. 1981 Mar 19;290(5803):261–264. doi: 10.1038/290261a0. [DOI] [PubMed] [Google Scholar]
  37. Shih C., Shilo B. Z., Goldfarb M. P., Dannenberg A., Weinberg R. A. Passage of phenotypes of chemically transformed cells via transfection of DNA and chromatin. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5714–5718. doi: 10.1073/pnas.76.11.5714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Shimizu K., Birnbaum D., Ruley M. A., Fasano O., Suard Y., Edlund L., Taparowsky E., Goldfarb M., Wigler M. Structure of the Ki-ras gene of the human lung carcinoma cell line Calu-1. Nature. 1983 Aug 11;304(5926):497–500. doi: 10.1038/304497a0. [DOI] [PubMed] [Google Scholar]
  39. Shimizu K., Goldfarb M., Perucho M., Wigler M. Isolation and preliminary characterization of the transforming gene of a human neuroblastoma cell line. Proc Natl Acad Sci U S A. 1983 Jan;80(2):383–387. doi: 10.1073/pnas.80.2.383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Tabin C. J., Bradley S. M., Bargmann C. I., Weinberg R. A., Papageorge A. G., Scolnick E. M., Dhar R., Lowy D. R., Chang E. H. Mechanism of activation of a human oncogene. Nature. 1982 Nov 11;300(5888):143–149. doi: 10.1038/300143a0. [DOI] [PubMed] [Google Scholar]
  41. Taparowsky E., Shimizu K., Goldfarb M., Wigler M. Structure and activation of the human N-ras gene. Cell. 1983 Sep;34(2):581–586. doi: 10.1016/0092-8674(83)90390-2. [DOI] [PubMed] [Google Scholar]
  42. Taparowsky E., Suard Y., Fasano O., Shimizu K., Goldfarb M., Wigler M. Activation of the T24 bladder carcinoma transforming gene is linked to a single amino acid change. Nature. 1982 Dec 23;300(5894):762–765. doi: 10.1038/300762a0. [DOI] [PubMed] [Google Scholar]
  43. Taub R., Kirsch I., Morton C., Lenoir G., Swan D., Tronick S., Aaronson S., Leder P. Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7837–7841. doi: 10.1073/pnas.79.24.7837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. 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]
  45. Willingham M. C., Pastan I., Shih T. Y., Scolnick E. M. Localization of the src gene product of the Harvey strain of MSV to plasma membrane of transformed cells by electron microscopic immunocytochemistry. Cell. 1980 Apr;19(4):1005–1014. doi: 10.1016/0092-8674(80)90091-4. [DOI] [PubMed] [Google Scholar]
  46. Yuasa Y., Srivastava S. K., Dunn C. Y., Rhim J. S., Reddy E. P., Aaronson S. A. Acquisition of transforming properties by alternative point mutations within c-bas/has human proto-oncogene. Nature. 1983 Jun 30;303(5920):775–779. doi: 10.1038/303775a0. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES