Oncogenes pp 3-24 | Cite as

Oncogenes and proto-oncogenes: General concepts

  • Chi V. Dang
Part of the Cancer Treatment and Research book series (CTAR, volume 47)


Theoretically, the cancerous phenotype of cells can result from epigenetic or biochemical regulatory changes without alteration of the genotype. Although epigenetic changes may contribute to neoplasia, overwhelming evidence supports the concept that neoplasia results from heritable changes allowing unrestrained growth of cells that are associated with altered expression of certain ‘cancer genes,’ or oncogenes [1,2]. The normal cellular counterparts that probably play some role in normal cell proliferation and differentiation are called proto-oncogenes. Genetic alterations (such as proviral insertional mutations, chromosomal translocation, gene amplification, or point mutations) can activate cellular oncogenes that in turn contribute to neoplasia.


Adenylyl Cyclase Tyrosine Kinase Activity Mouse Mammary Tumor Virus Viral Oncogene Cellular Oncogene 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Varmus HE: Cellular and viral oncogenes. In: Stamatoyannopoulos G, Nienhuis AW, Leder P, Majerus PW (eds): The Molecular Basis of Blood Diseases. Philadelphia, WB Saunders, 1987, pp 271–346.Google Scholar
  2. 2.
    Bishop JM: The molecular genetics of cancer. Science 235:305–311, 1987.PubMedCrossRefGoogle Scholar
  3. 3.
    Baserga R: The Biology of Cell Reproduction. Cambridge, Havard University Press, 1985.Google Scholar
  4. 4.
    Sporn MB, Roberts AB: Peptide growth factors are multifunctional. Nature 332:217–219, 1988.PubMedCrossRefGoogle Scholar
  5. 5.
    Evans RM: The steroid and thyroid hormone receptor superfamily. Science 240:889–895, 1988.PubMedCrossRefGoogle Scholar
  6. 6.
    Hanks SK, Quinn AM, Hunter T: The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science 241:42–52, 1988.PubMedCrossRefGoogle Scholar
  7. 7.
    Hunter T, Cooper JA: Protein tyrosine kinases. Annu Rev Biochem 54:897–930, 1985.PubMedCrossRefGoogle Scholar
  8. 8.
    Sherr CJ: Growth factor receptor and cell transformation. Mol Biol Med 4:1–10, 1987.PubMedGoogle Scholar
  9. 9.
    Czech MP, Klarlund JK, Yagaloff KA, Bradford AP, Lewis RE: Insulin receptor signalling. J Biol Chem 263:11017–11020, 1988.PubMedGoogle Scholar
  10. 10.
    Yarden Y, Ullrich A: Molecular analysis of signal transduction by growth factors. Biochemistry 27:3113–3119, 1988.PubMedCrossRefGoogle Scholar
  11. 11.
    Majerus PW, Connolly TM, Bansal VS, Inhorn RC, Ross TS, Lips DL: Inositol phophates: synthesis and degradation. J Biol Chem 263:3051–3054.Google Scholar
  12. 12.
    Kikkawa U, Nishizuka Y: Role of protein kinase C in transmembrane signalling. Annu Rev Cell Biol 2:149–178, 1986.PubMedCrossRefGoogle Scholar
  13. 13.
    Roesler WJ, Vanderbark GR, Hanson RW: Cyclic AMP and the induction of eukaryotic gene expression. J Biol Chem 263:9063–9066, 1988.PubMedGoogle Scholar
  14. 14.
    Neer EJ, Clapham DE: Roles of G protein subunits in transmembrane signalling. Nature 333:129–134, 1988.PubMedCrossRefGoogle Scholar
  15. 15.
    Gilman AG: G proteins: transducers of receptor-generated signals. Annu Rev Biochem 56:615–649, 1987.PubMedCrossRefGoogle Scholar
  16. 16.
    Casey PJ, Gilman AG: G protein involvement in receptor-effector coupling. J Biol Chem 263:2577–2580, 1988.PubMedGoogle Scholar
  17. 17a.
    Cales C, Hancock JF, Marshall CJ, Hall: The cytoplasmic protein GAP is implicated as the target for regulation by the ras gene product. Nature 332:548, 1988.PubMedCrossRefGoogle Scholar
  18. 17b.
    Cales C, Hancock JF, Marshall CJ, Hall: The cytoplasmic protein GAP is implicated as the target for regulation by the ras gene product. Nature 332:551, 1988.CrossRefGoogle Scholar
  19. 18.
    Rozengurt E: Early signals in the mitogenic response. Science 234:161–166, 1986.PubMedCrossRefGoogle Scholar
  20. 19.
    Perona R, Serrano R: Increased pH and tumorigenicity of fibroblasts expressing a yeast proton pump. Nature 334:438–440, 1988.PubMedCrossRefGoogle Scholar
  21. 20.
    Klee CB, Gouch TH, Richman PG: Calmodulin. Annu Rev Biochem 49:489–515, 1980.CrossRefGoogle Scholar
  22. 21.
    McKnight S, Tjian R: Transcriptional selectivity of viral genes in mammalian cells. Cell 46:795–805, 1986.PubMedCrossRefGoogle Scholar
  23. 22.
    Ryder K, Lau LF, Nathans D: A gene activated by growth factors is related to the oncogene v-jun. Proc Natl Acad Sci USA 85:1487–1491, 1988.PubMedCrossRefGoogle Scholar
  24. 23.
    Varmus HE: Retroviruses. Science 240:1427–1435, 1988.PubMedCrossRefGoogle Scholar
  25. 24.
    Levine AJ: Oncogenes of DNA tumor viruses. Cancer Res 48:493–496, 1988.PubMedGoogle Scholar
  26. 25.
    Colledge WH, Richardson WD, Edge MD, Smith AE: Extensive mutagenesis of the nuclear location signal of simian virus 40 large T antigen. Mol Cell Biol 8:2177–2183, 1986.Google Scholar
  27. 26.
    Velcich A, Ziff E: Adenovirus Ela ras cooperation activity is separate from its positive and negative transcription regulating functions. Mol Cell Biol 8:2177–2183, 1988.PubMedGoogle Scholar
  28. 27.
    Whyte P, Buchkovich KJ, Horowitz JM, Friend SH, Raybuch M, Weinberg RA, Harlow E: Association between an oncogene and an anti-oncogene: the adenovirus El A products bind to the retinoblastoma gene product. Nature 334:124–129, 1988.PubMedCrossRefGoogle Scholar
  29. 28.
    DeCaprio JA, Ludlow JW, Figge J, Shew JY, Huang CM, Lee WH, Marsilio E, Paucha E, Livingston D: SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell 54:275–283, 1988.PubMedCrossRefGoogle Scholar
  30. 29.
    Yoshida M, Seiki M: Recent advances in the molecular biology of HTLV-1: transactivation of viral and cellular genes. Annu Rev Immunol 5:541–559, 1987.PubMedCrossRefGoogle Scholar
  31. 30.
    Shih C, Shilo B, Goldfarb MP, Dannenberg A, Weinberg RA: Passage of phenotypes of chemically transformed cells via transfection of DNA and chromatin. Proc Natl Acad Sci USA 76:5714–5718, 1979.PubMedCrossRefGoogle Scholar
  32. 31.
    Nishimura S, Sekiya T: Human cancer and cellular oncogenes. Biochem J 243:313–327, 1987.PubMedGoogle Scholar
  33. 32.
    Tsujimoto Y, Cossman J, Jaffe E, Croce CM: Involvement of the bcl-2 gene in human follicular lymphoma. Science 228:1440–1443, 1985.PubMedCrossRefGoogle Scholar
  34. 33.
    Tsujimoto Y, Jaffe E, Cossman J, Gorham J, Nowell PC, Croce CM: Clustering of break-points on chromosome 11 in human B-cell neoplasms with the t[ll;14] chromosome translocation. Nature 315:340–343, 1985.PubMedCrossRefGoogle Scholar
  35. 34.
    Morton CC, Duby AD, Eddy RL Show TB, Seidman JG: Genes for beta gene of human T-cell antigen receptor map to regions of chromosomal rearrangement in T cells. Science 228:582–585, 1985.PubMedCrossRefGoogle Scholar
  36. 35.
    Lewis WH, Michalopoulos EE, Williams DL, Minden MD, Mak TW: Breakpoints in the human T-cell antigen receptor alpha-chain locus in two T-cell leukaemia patients with chromosomal translocations. Nature 317:544–546, 1985.PubMedCrossRefGoogle Scholar
  37. 36.
    Doolittle RF, Hunkapiller MW, Hood LE, Devare SG, Robbins KC, Aaronson SA, Antonaides HN: Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science 221:275–277, 1983.PubMedCrossRefGoogle Scholar
  38. 37.
    Keating MT, Williams LT: Autocrine stimulation of intracellular PDGF receptors in v-sis transformed cells. Science 239:914–916, 1988.PubMedCrossRefGoogle Scholar
  39. 38.
    Rijsewijk F, Schuermann M, Wagenaar E, Parren P, Weigel D, Nusse R: The Drosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless. Cell 50:649–657, 1987.PubMedCrossRefGoogle Scholar
  40. 39.
    Jaye M, Lyall RM, Mudd R, Schlessinger J, Sarver N: Expression of acidic fibroblast growth factor cDNA confers growth advantage and tumorigenesis to Swiss 3T3 cells. EMBO J 7:963–969, 1988.PubMedGoogle Scholar
  41. 40.
    Delli Bovi P, Curatola AM, Kern FG, Breco A, Ittman M, Basilico C: An oncogene isolated by transfection of Kaposi’s sarcoma DNA encodes a growth factor. Cell 50:729–737, 1987.CrossRefGoogle Scholar
  42. 41.
    Taira M, Yoshida T, Miyagawa K, Sakamoto H, Terada M, Sugimara T; cDNA sequence of human transforming gene hst and identification of the coding sequence required for transforming activity. Proc Natl Acad Sci USA 84:2980–2984, 1987.PubMedCrossRefGoogle Scholar
  43. 42.
    Downward J, Yarden Y, Mayes E, Scrace G, Totty N, Stockwell P, Ullrich A, Schlessinger J, Waterfield MD: Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature 307:521–527, 1984.PubMedCrossRefGoogle Scholar
  44. 43.
    Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/ner oncogene. Science 235:177–182, 1987.PubMedCrossRefGoogle Scholar
  45. 44.
    Sieff CA: Hematopoietic growth factors. J Clin Invest 79:1549–1557, 1987.PubMedCrossRefGoogle Scholar
  46. 45.
    Sherr CJ, Rettenmier CW, Sacca R, Roussel MF, Look AT, Stanley ER: The c-fms protooncogene product is related to the receptor for the mononuclear phagocyte growth factor CSF-1. Cell 41:665–676, 1985.PubMedCrossRefGoogle Scholar
  47. 46.
    Birchmeier C, Sharma S, Wigler M: Expression and rearrangement of the ROSI gene in human glioblastoma cells. Proc Natl Acad Sci USA 84:9270–9274, 1987.PubMedCrossRefGoogle Scholar
  48. 47.
    Oskam R, Coulier F, Ernst M, Martin-Zanca D, Barbacid M: Frequent generation of oncogenes by in vitro recombination of Trk protooncogene sequences. Proc Natl Acad Sci USA 85:2964–2968, 1988.PubMedCrossRefGoogle Scholar
  49. 48.
    Wang LH, Lin B, Jong SMJ, Dixon D, Ellis L, Roth RA, Rutter WJ: Activation of transforming potential of the human insulin receptor gene. Proc Natl Acad Sci USA 84:5725–5729, 1987.PubMedCrossRefGoogle Scholar
  50. 49.
    Kozma SC, Redmond SMS, Xiao-Chang F, Saurer SM, Groner B, Hynes NE: Activation of the receptor kinase domain of the trk oncogene by recombination with two cellular sequences. EMBO J 7:147–154, 1988.PubMedGoogle Scholar
  51. 50.
    Kamps MP, Buss JE, Sefton BM: Rous sarcoma virus transforming protein lacking myristic acid phosphorylates known peptide substrates without inducing transformation. Cell 45: 105–112, 1986.PubMedCrossRefGoogle Scholar
  52. 51.
    Dreazen O, Canaani E, Gale RP: Molecular biology of chronic myelogenous leukemia. Semin Hematol 25:35–49, 1988.PubMedGoogle Scholar
  53. 52.
    Daley GQ, McLaughlin J, Witte ON, Baltimore D: The CML-specific P210 bcr/abl protein, unlike v-abl, does not transform NIH/3T3 fibroblasts. Science 237:532–535, 1987.PubMedCrossRefGoogle Scholar
  54. 53.
    Edelman AM, Blumenthal DK, Krebs EG: Protein serine/threonine kinases. Annu Rev Biochem 56:567–613, 1987.PubMedCrossRefGoogle Scholar
  55. 54.
    Kasid U, Pfeifer A, Weichselbaum RR, Dritschilo A, Mark GE: The raf oncogene is associated with a radiation-resistant human laryngeal cancer. Science 237:1039–1041, 1987.PubMedCrossRefGoogle Scholar
  56. 55.
    Stanton VP, Cooper GM: Activation of human raf transforming genes by deletion of normal amino-terminal coding sequences. Mol Cell Biol 7:1171–1179, 1987.PubMedGoogle Scholar
  57. 56.
    Seith A, Priel E, Vande Woude GF: Nucleotide triphosphate-dependent DNA-binding properties of mos protein. Proc Natl Acad Sci USA 84:3560–3564, 1987.CrossRefGoogle Scholar
  58. 57.
    Barbacid M: ras genes. Annu Rev Biochem 56:779–827, 1987.PubMedCrossRefGoogle Scholar
  59. 58.
    Bos JL, Fearon ER, Hamilton SR, Verlaan-deVries M, van Boom JH, van der Eb AT, Volgelstein B: Prevalence of ras gene mutations in human colorectal cancers. Nature 327:293–297, 1987.PubMedCrossRefGoogle Scholar
  60. 59.
    de Vos A, Tong L, Milburn MV, Matias PM, Jancarik J, Noguchi S, Nishimura S, Miura K, Ohtsuka E, Kim SH: Three dimensional structure of an oncogene protein: catalytic domain of human c-H-ras p21. Science 239:888–893, 1988.PubMedCrossRefGoogle Scholar
  61. 60.
    Toda T, Uno I, Ishikawa T, Powers S, Kataoka T, Broek D, Cameron S, Broach J, Matsumoto K, Wigler M: In yeast, RAS proteins are controlling elements of adenylate cyclase. Cell 40:27–36, 1985.PubMedCrossRefGoogle Scholar
  62. 61.
    Schmitt HD, Wagner P, Pfaff E, Gallwitz D: The ras-related YPT1 gene product in yeast: a GTP-binding protein that might be involved in microtubule organization. Cell 47:401–412, 1986.PubMedCrossRefGoogle Scholar
  63. 62.
    Alt FW, Harlow E, Ziff EB: Nuclear Oncogenes. Current Communications in Molecular Biology. Cold Spring Harbor, NY, Cold Spring Harbor Laboratory, 1987.Google Scholar
  64. 63.
    Dang CV, Lee WMF: Identification of the human c-myc protein nuclear translocation signal. Mol Cell Biol 8:4048–4054, 1988.PubMedGoogle Scholar
  65. 64.
    Gilmore TD, Temin HM: v-rel oncoproteins in the nucleus and cytoplasm transform chicken spleen cells. J Virol 62:703–714, 1988.PubMedGoogle Scholar
  66. 65.
    Franza BR JR, Rauscher III FJ, Josephs SF, Curran T: The Fos complex and Fos-related antigens recognize sequence elements that contain API binding sites. Science 239:1150–1153, 1988.PubMedCrossRefGoogle Scholar
  67. 66.
    Bohmann D, Bos TJ, Admon A, Nishimura T, Vogt PK, Tjian R: Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1. Science 238:1386–1392, 1988.CrossRefGoogle Scholar
  68. 67.
    Angel P, Allegretto EA, Okino ST, Hattori K, Boyle WT, Hunter T, Karin M: Oncogene jun encodes a sequence-specific trans-activator similar to AP-1. Nature 332:166–170, 1988.PubMedCrossRefGoogle Scholar
  69. 68.
    Landshulz WH, Johnson PF, McKnight SL: The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins. Science 240:1759–1764, 1988.CrossRefGoogle Scholar
  70. 69.
    Weinberger C, Thompson EC, Ong ES, Lebo R, Gruol DJ, Evans RM: The c-erb-A gene encodes a thyroid hormone receptor. Nature 324:641–646, 1986.PubMedCrossRefGoogle Scholar
  71. 70.
    Munoz A, Zenke M, Gehring U, Sap J, Beug H, Vennstrom B: Characterization of the hormone-binding domain of the chicken c-erb-A/thyroid hormone receptor protein. EMBO J 7:155–159, 1988.PubMedGoogle Scholar
  72. 71.
    Zenke M, Kahn P, Disela C, Vennstrom B, Lentz A, Keegan K, Hayman MJ, Choi HR, Yew N, Engel JD, Beug H: v-erb-A specifically suppresses transcription of the avian anion transporter (band 3) gene. Cell 53:107–119, 1988.CrossRefGoogle Scholar
  73. 72.
    Kahn P, Fryberg L, Brady C, Stanley IJ, Beug H: v-erb-A cooperates with sarcoma oncogenes in leukemia cell transformation. Cell 45:349–356, 1986.PubMedCrossRefGoogle Scholar
  74. 73.
    Temin HM: Evolution of cancer genes as a mutation-driven process. Cancer Res 48: 1697–1701, 1988.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1989

Authors and Affiliations

  • Chi V. Dang

There are no affiliations available

Personalised recommendations