• Matthias H. Kraus


Cancer arises from the progressive accumulation of genetic lesions that are somatically acquired or, in certain instances, present in the genuline. Two major categories of genes including proto-oncogenes and suppressor genes, are affected. They can be distinguished according to positive or negative regulatory properties exerted on cell growth by their corresponding gene products. Genetic changes converting proto-oncogenes to oncogenes result in constitutive gain of function of the gene product and consequently exert a dominant effect on phenotype. Mutations resulting in loss of function of suppressor genes determine phenotype usually in a recessive manner but can sometimes gain dominant properties. Proto-oncogene activation and inactivation of suppressor gene function both contribute to the lack of growth control and unrestrained proliferation characteristic of tumor cells [1, 2]. Direct corroboration of the genetic basis of cancer originated from observations emerging from studies of acute transforming retroviruses, which led to the identification of oncogenes. The normal counterparts of oncogenes comprise a limited number of evolutionarily conserved molecules (ie, proto-oncogenes) that are frequently activated as cellular oncogenes (c-onc) independent of retroviruses in spontaneous human cancer. Proto-oncogenes encode proteins residing at decisive checkpoints within a complex cellular signaling network controlling growth and proliferation. Under physiologic conditions, they integrate growth programs of a cell in response to extracellular signals and thereby exert control on the homeostasis of metazoan organisms. Subversion of their physiologic control function by activation to cellular oncogenes represents an intricate component in the pathogenesis of cancer [3].


Epidermal Growth Factor Receptor Gene Rearrangement Epidermal Growth Factor Receptor Gene Familial Medullary Thyroid Carcinoma Cellular Oncogene 
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  1. 1.
    Knudson AG: Antioncogenes and human cancer. Proc Natl Acad Sci USA 1993, 90: 10914–10921.PubMedCrossRefGoogle Scholar
  2. 2.
    Weinberg RA: Oncogenes and tumor suppressor genes. CA Cancer J Clin 1994, 44: 160–170.PubMedCrossRefGoogle Scholar
  3. 3.
    Hunter T: Oncoprotein networks. Cell 1997, 88: 333–346.PubMedCrossRefGoogle Scholar
  4. 4.
    Weiss R, Teich N, Varmus H, Coffin J: RNA Tumor Viruses. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press; 1985.Google Scholar
  5. 5.
    Weiss RA, Teich N, Varmus H, Coffin J: Molecular Biology of Tumor Viruses. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press; 1984.Google Scholar
  6. 6.
    Lewin B: Genes V. New York: Oxford University Press; 1994.Google Scholar
  7. 7.
    Bishop JM: Molecular themes in oncogenesis. Cell 1991, 64: 235–248.PubMedCrossRefGoogle Scholar
  8. 8.
    Hunter T: Cooperation between oncogenes. Cell 1991, 64: 249–270.PubMedCrossRefGoogle Scholar
  9. 9.
    McCormick F: Signal transduction: how receptors turn Ras on. Nature 1993, 363: 15–16.PubMedCrossRefGoogle Scholar
  10. 10.
    Aaronson SA: Growth factors and cancer. Science 1991, 254: 1146–1153.PubMedCrossRefGoogle Scholar
  11. 11.
    Sherr CJ: Cancer cell cycles. Science 1996, 274: 1672–1677.PubMedCrossRefGoogle Scholar
  12. Alberts B, Bray D, Lewis J, et al.: Molecular Biology of the Cell. New York: Garland Publishing; 1994.Google Scholar
  13. Schmidt L, Duh FM, Chen F, et al.: Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat Genet 1997, 16:68–73.Google Scholar
  14. 14.
    Cross M, Dexter TM: Growth factors in development, transformation, and tumorigenesis. Cell 1991, 64: 271–280.PubMedCrossRefGoogle Scholar
  15. 15.
    Schlessinger J: Signal transduction by allosteric receptor oligomerization. Trends Biochem Sci 1988, 13: 443–447.PubMedCrossRefGoogle Scholar
  16. 16.
    Heldin CH: Dimerization of cell surface receptors in signal transduction. Cell 1995, 80: 213–223.PubMedCrossRefGoogle Scholar
  17. Nagata K, Ohashi K, Nakano T, et al.: Identification of the product of growth arrest-specific gene 6 as a common ligand for Axl, Sky, and Mer receptor tyrosine kinases. J Biol Chem 1996, 271:30022–30027.Google Scholar
  18. Treanor JJ, Goodman L, de Sauvage F, et al.: Characterization of a multicomponent receptor for GDNF [comments]. Nature 1996, 382:80–83.Google Scholar
  19. 19.
    Tessier-Lavigne M: Eph receptor tyrosine kinases, axon repulsion, and the development of topographic maps. Cell 1995, 82: 345–348.PubMedCrossRefGoogle Scholar
  20. 20.
    van der Geer P, Hunter T, Lindberg RA: Receptor protein-tyrosine kinases and their signal transduction pathways. Annu Rev Cell Biol 1994, 10: 251–337.PubMedCrossRefGoogle Scholar
  21. 21.
    Di Fiore PP, Kraus MH: Mechanisms involving an expanding erbB/EGF receptor family of tyrosine kinases in human neoplasia. In Genes, Oncogenes, and Hormones: Advances in Cellular and Molecular Biology of Breast Cancer. Edited by Dickson RB, Lippman ME. Boston: Kluwer Academic Publishers; 1991: 139–160.Google Scholar
  22. 22.
    Mak YF, Ponder BA: RET oncogene. Curr Opin Genet Dev 1996, 6: 82–86.PubMedCrossRefGoogle Scholar
  23. 23.
    Boguski MS, McCormick F: Proteins regulating Ras and its relatives. Nature 1993, 366: 643–654.PubMedCrossRefGoogle Scholar
  24. 24.
    Rabbitts TH: Chromosomal translocations in human cancer. Nature 1994, 372: 143–149.PubMedCrossRefGoogle Scholar
  25. 25.
    Pawson T: New impressions of Src and Hck [news; comment]. Nature 1997, 385:582–583,585.PubMedCrossRefGoogle Scholar
  26. 26.
    Farrow SN, Brown R: New members of the Bc12 family and their protein partners. Curr Opin Genet Dev 1996, 6: 45–49.PubMedCrossRefGoogle Scholar
  27. 27.
    Lewin B: Oncogenic conversion by regulatory changes in transcription factors. Cell 1991, 64: 303–312.PubMedCrossRefGoogle Scholar
  28. 28.
    Weinberg RA: The cat and mouse games that genes, viruses, and cells play. Cell 1997, 88: 573–575.PubMedCrossRefGoogle Scholar
  29. 29.
    Weinberg RA: Oncogenes, antioncogenes, and the molecular basis of multistep carcinogenesis. Cancer Res 1989, 49: 3713–3721.PubMedGoogle Scholar
  30. 30.
    Levine AJ: p53, the cellular gatekeeper for growth and division. Cell 1997, 88:323–331.CrossRefGoogle Scholar
  31. 31.
    Marshall CJ: Tumor suppressor genes. Cell 1991, 64: 313–326.PubMedCrossRefGoogle Scholar
  32. 32.
    Peifer M: Beta-catenin as oncogene: the smoking gun [comment]. Science 1997, 275: 1752–1753.PubMedCrossRefGoogle Scholar
  33. 33.
    Fearon ER, Vogelstein B: A genetic model for colorectal tumorigenesis. Cell 1990, 61: 759–767.PubMedCrossRefGoogle Scholar
  34. 34.
    Statement of the American Society of Clinical Oncology: Genetic testing for cancer susceptibility, Adopted on February 20,1996. J Clin Oncol 14: 1730–1740.Google Scholar
  35. 35.
    Sklar J: Principles of molecular cell biology of cancer: molecular approaches to cancer diagnosis. In Cancer: Principles and Practice of Oncology. Edited by De Vita VT, Hellman S, Rosenberg SA. Philadelphia: JB Lippincott; 1993: 92–113.Google Scholar
  36. 36.
    Kraus MH, Popescu NC, Amsbaugh SC, King CR: Overexpression of the EGF receptor-related proto-oncogene erbB-2 in human mammary tumor cell lines by different molecular mechanisms. EMBO J 1987, 6: 605–610.PubMedGoogle Scholar
  37. Alimandi M, Romano A, Curia MC, et al.: Cooperative signaling of ErbB3 and ErbB2 in neoplastic transformation and human mammary carcinomas. Oncogene 1995, 10:1813–1821.Google Scholar
  38. Santoro M, Carlomagno F, Romano A, et al.: Activation of RET as a dominant transforming gene by germline mutations of MEN2A and MEN2B. Science 1995, 267:381–383.Google Scholar
  39. 39.
    Kraus MH, Yuasa Y, Aaronson SA: A position 12-activated H-ras oncogene in all HS578T mammary carcinosarcoma cells but not normal mammary cells of the same patient. Proc Natl Acad Sci USA 1984, 81: 5384–5388.PubMedCrossRefGoogle Scholar
  40. 40.
    Graus-Porta D, Beerli RR, Daly JM, Hynes NE: ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. Embo J 1997, 16: 1647–1655.PubMedCrossRefGoogle Scholar

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© Current Medicine, Inc. 2000

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  • Matthias H. Kraus

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