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Cancer - Facts, Dilemmas and Mysteries

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Anticarcinogenesis and Radiation Protection 2

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Abstract

Cancer is a disease of multifactorial etiology. Chemical, physical and viral environmental factors are involved in carcinogenesis. Numerous mutagenic events are required to transform a normal cell into a malignant one (1, 2). There is a high correlation between cancer and traumatic psychosocial events (3, 4). Carcinogenesis is a consequence of imbalances in the regulatory mechanisms that normally control the gene expression or function of the growth factors, receptors, and pathways of signal transduction. Chemical and physical carcinogens may induce cancer by altering the structure and functions of cellular protooncogenes. The viruses, however, transform cells either directly through an active viral oncogene or, if they lack oncogene, they may transform the cell by insertion of viral promoter sequences near or within the protooncogenes that would cause activation of protooncogene transcription and expression (2, 5-17). Discovery of oncogenes and their expression, as well as identification of their products, has thus revolutionized our approach to the molecular and genetic basis of multistage carcinogenesis. Protooncogenes normally code for proteins that play a role in the regulation of gene expression and at various stages of the action of growth factors during development and differentiation. These cellular protooncogenes do not seem to be tumorigenic themselves but must rather be activated by mutations and/or aberrant signal transduction and abnormal gene expression (1-17). The genes that code for receptors or components of signal transducing mechanisms, as well as for steroids, prolactin prostaglandins and other growth factors, should be considered as protooncogenes too, since the alteration of their functioning may contribute to abnormal growth and tumorigenesis (2,4,5,14,15). Malignant cells are immortalized, live longer than normal cells and fail to undergo normal differentiation. Their growth is autonomous, self-stimulated by autocrine secretion of various growth factors (2, 5-7). Immortalization seems to be associated with increased transcription of myc, myb, fos, jun oncogenes (2,5,6,8-11,13-17) and with the large T-gene of polyoma virus (5, 12).

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References

  1. M. Meselson and K. Russel; Comparison of carcinogenic and mutagenic potency, In “Origins of Human Cancer” 1977 (H.H. Hiat, J.D.Watson and J.A.Winsten, Eds), p.1473. Cold Spring Harbor Symp, New York

    Google Scholar 

  2. J. M. Bishop, The molecular genetics of cancer. Science 235,305(1987)

    Google Scholar 

  3. R. Grossarth-Maticek, D. T. Kanazir, H. Vetter, P. Schmidt, Psychosomatic factors involved in the process of carcinogenesis. Psychother. Psychosomat. 40,191 (1983)

    Article  CAS  Google Scholar 

  4. D. T. Kanazir, R. Djordjevic-Markovic, R. Grossarth-Maticek, Psychosocial (emotional) stress, steroid hormones and carcinogenesis. Molecular aspects, facts and speculations. In “Progress in Bioorganic Chemistry and Molecular Biology,” 1985 (Yu. A.Ovchinnikov, Ed.) p.509. Elsevier Science Publishers, Amsterdam

    Google Scholar 

  5. D. Weinstein, Growth factors, oncogenes and multistage carcinogenesis. J Cell. Biochem. 22,213 (1987)

    Article  Google Scholar 

  6. P. Newmark, Cancer genes, processed genes, jumping genes. Nature 296,393 (1981)

    Article  Google Scholar 

  7. A. S. Goustin, E. G. Leof, G. D. Shipley and H. L. Moses, Growth factors and cancer. Cancer Res. 46,1015 (1986)

    PubMed  CAS  Google Scholar 

  8. R. E. Kingston, A. S. Baldwin and P. A. Sharp, Transcription control by oncogenes. Cell. 41,3 (1983)

    Article  Google Scholar 

  9. K. Alitalo, G. Ramshy, J. M. Bishop, O. S. Pfeifer, W. W. Colby and A. D. Levinson, Identification of nuclear proteins encoded by viral and cellular myc oncogenes. Nature 306,274 (1983)

    Article  PubMed  CAS  Google Scholar 

  10. G. P. Studzinski, C. S. Brelvi, R. A. Wat, Participation of c-myc protein in DNA synthesis of human cells. Science 234,467 (1986)

    Article  PubMed  CAS  Google Scholar 

  11. M. Robertson, Progress in malignancy, Nature 309,512 (1984)

    Article  PubMed  CAS  Google Scholar 

  12. M. Rassoulzadegan, Y. Naghashfar, A. Cowie, A. Carr, et.al., Expression of the large T protein of polyoma virus promotes the establishment in culture of “normal” rodent fibroblast cell lines. Proc. Natl. Acad. Sci. (USA) 80,4354 (1983)

    Article  CAS  Google Scholar 

  13. K. Kelly, B. H. Cochran, C. D. Stiles, P. Leder, Cell-specific regulation of the c-myc gene. Cell 35,603 (1983)

    Article  PubMed  CAS  Google Scholar 

  14. K. B. Burck, E. T. Liu, J. W. Larrick, Oncogenes. Springer-Verlag, New York Inc.(1988)

    Book  Google Scholar 

  15. S. Saule and D. Leprince, Oncogenes, In “Retroviruses and Oncogenes,” 1988 (M. Crepin, Ed.), p.169. John Libbey, Eurotext,London,Paris

    Google Scholar 

  16. H. E. Varmus, Form and function of retroviral proviruses, Science 216,812 (1982)

    Article  PubMed  CAS  Google Scholar 

  17. J. M. Bishop and H. E. Varmus. Molecular biology of tumor viruses 1985 (R.A. Weiss et al. Eds.) Cold Spring Harbor Press, Part I p.249. Cold Spring Harbor, N.Y.

    Google Scholar 

  18. Y. K. T. Fung, W. G. Lewis, M. J. Hung, B. L. Crittenden, Activation of the cellular c-erbB by LTR insertion. Cell 33,657 (1983)

    Article  Google Scholar 

  19. M. A. Raisnes, W. C. Lewis, L. B. Crittenden, H. Kung, c-erb B activation in avian leukosis virus induced erythroblastosis; clustered integration sites and the arrangement of proviruses in c-erbB alleles. Proc. Natl. Acad. Sci. (USA) 82,2287 (1985)

    Article  Google Scholar 

  20. J. B. Levy, H. Iba, H. Hanafusa, Activation of the transforming potential of p.60 c-src by a single amino acid changes. Proc. Natl. Acad. Sci. (USA) 83,4228 (1986)

    Article  CAS  Google Scholar 

  21. F. J. Tofilon, N. Buckley and D. F. Deen, Homologies between signal transducing G-proteins and ras-gene products. Science 226,860 (1984)

    Article  Google Scholar 

  22. J. P. McGrath, D. J. Capon, V. D. Goeddel, D. A. Levinson, Comparative biological properties of normal and activated human ras p21 protein. Nature 310,644 (1981)

    Article  Google Scholar 

  23. S. W. Hayward, B. G. Neel, S. M. Astrin, Activation of a cellular oncogene by promoter insertion in ALV induced lymphoid lenkosis. Nature 290,475 (1981)

    Article  PubMed  CAS  Google Scholar 

  24. M. R. Noari-Daloii, R. A. Swift and H. J. Kung, Specific integration of REV proviruses in avian bursal lymphoma. Nature 294,574 (1981)

    Article  Google Scholar 

  25. S. G. Payne, J. H. Bishop, E. H. Varmus, Multiple arrangements of viral DNA and an activated host oncogenes in bursal lymphoma. Nature 295,209 (1982)

    Article  PubMed  CAS  Google Scholar 

  26. D. Westway, G. Payng, H. E. Varmus, Proviral deletions and oncogene base-substitutions in insertionally mutagenized c-myc alleles may contribute to progression of avian tumors. Proc. Natl. Acad. Sci. (USA) 11,843 (1984)

    Article  Google Scholar 

  27. V. Manne, E. Bekesi and H. F. Kung, Ha-ras proteins exhibit GTP-ase activity: point mutations that activate Ha-ras products result in decreased GTP-ase activity. Proc. Natl. Acad. Sci. (USA) 82,376 (1985)

    Article  CAS  Google Scholar 

  28. P. Kahn, L. Frykberg, C. Brady, I. Stanley, et al., v-erbA Cooperates with sarcoma oncogenes in leukemic cell transformation. Cell 45, 349 (1986)

    Article  PubMed  CAS  Google Scholar 

  29. C. Setoyama, R. Frunzio, M. Mudryj and B. Crombrugghe, Transcriptional activation encoded by the V-fos gene. Proc. Natl. Acad. Sci. (USA) 83,3213 (1986)

    Article  CAS  Google Scholar 

  30. T. Hunter and J. A. Cooper, Protein tyrosine kinase. Annu. Rev. Biochem. 54,897 (1985)

    Article  PubMed  CAS  Google Scholar 

  31. P. L. Kaplan, M. Anderson, B. Ozanne, Transforming growth factor(s) production enables cells to grow in the absence of serum; an autocrine system. Proc. Natl. Acad. Sci. (USA) 79,485 (1982)

    Article  CAS  Google Scholar 

  32. G. J. Todaro, C. Fryling, J. E. De Larco, Transforming growth factors produced by certain human tumor cells: Polypeptides that interact with epidermal growth factor receptors. Proc. Natl, Acad., Sci. (USA) 77,5258 (1980)

    Article  CAS  Google Scholar 

  33. M. B. Sporn, A. B. Roggert, Autocrine growth factors and cancer. Nature 313,745 (1985)

    Article  PubMed  CAS  Google Scholar 

  34. R. Derynck, Transforming growth factor alpha structure and biological activities. J. Cell. Biochem. 22,293 (1986)

    Article  Google Scholar 

  35. D. T. Kanazir, B. Fasciotto, V. Krsmanovic, Activite mitogene de facteurs secretes par des cellules transformes par les virus de l’erythroblastose aviaire. C.R. Acad. Sci. (Paris) 202,63 (1986)

    Google Scholar 

  36. B. Fascitto, D. T. Kanazir, J. P. Durkin, J. F. Whitfield, and V. Krsmanovic, AEV-transformed chicken erythroid cells secrete autocrine factors which promote soft agar growth and block erythroleukemia cells differentiation. Biochem. Biophys, Res. Commun. 143,175 (1987)

    Google Scholar 

  37. B. Fasciotto, D. T. Kanazir, J. P. Durkin, J. F. Whitfield, V. Krsmanovic, Blockade of erythroleukemia cell induced differentiation by autocrine growth factor(s). In “The Inhibitors of hematopoiesis,” 1987 (A. Nayman, M. Guigon, N.C. Gorin, J.Y. Mary, Eds) p.201. John Libbey, Eurotext, London and Paris

    Google Scholar 

  38. V. Krsmanovic, N. Morarjet, J. M. Biquard, G. Mouchrot, B. Fasciotto, A. Ristic, C. Parmentier, J. P. Blanchet, D. T. Kanazir, J. P. Durkin, J. F. Whitfieled, Autocrine differentiation - Inhibiting factor from chicken erythroleukemia cells on human and mouse early BFU-E erythroid progenitors. Biochem. Biophys. Res. Commun. 157,782 (1988)

    Article  Google Scholar 

  39. T. Bringman, P. B. Lindquist, R. Derynck, Different transforming growth factor-alpha species are derived from a glycosylated and palmitoylated transmembrane precursor. Cell 48,429 (1987)

    Article  PubMed  CAS  Google Scholar 

  40. R. Derynck, A. B. Rogerts, E. M. Trinreler et al., Human transforming growth factor precursor structure and expression in E cola. Cell 38,287 (1984)

    Article  PubMed  CAS  Google Scholar 

  41. M. D. Waterfield, G. T. Scrace, N. Whittle et al. Platelet-derived growth facto is structurally related to the putative transforming protein p28s s of simian sarcoma virus. Nature 304,35 (1983)

    Article  PubMed  CAS  Google Scholar 

  42. C. D. Rao, H. Igarashi, I. M. Chiu, et al. Structure and sequence of the human c-sis/platelet-derived growth factor 2 (SIS/PDGF2) transcriptional unit. Proc. Natl., Acad. Sci. (USA) 83,2392 (1986)

    Article  CAS  Google Scholar 

  43. F. Cuttita, D. N. Carney, J. Mulshine, et al., Bombesin-like peptides can function as autocrine growth factors in human small cell lung cancer. Nature 316,823 (1985)

    Article  Google Scholar 

  44. R. K. Assoin, Transforming factor: biological function and chemical structure. Science 239,532 (1986)

    Google Scholar 

  45. J. H. Kehrl, M. A. Mon, A. S. Fauci, Type beta transforming growth factor suppresses the growth and differentiation of human B and T-lymphocytes. Clin. Res. 33,610 (1985)

    Google Scholar 

  46. D. A. Lawrence, Transforming growth factor beta: a multifunctional growth regulator. In “Malignant Cell Secretion,” 1990 (V. Krsmanovic and J.F. Whitefield, Eds). CRC Press, Inc. Boca Raton

    Google Scholar 

  47. Y. Yarden, J. A. Escobedo, J. W. Kuang et al., Structure of the receptor for platelet-derived growth factors helps define a family of closely related growth factor receptors. Nature 323,226 (1986)

    Article  PubMed  CAS  Google Scholar 

  48. J. Downward, Y. Yarden, E. Mayes, et al., Close similarity of epidermal growth factor receptor and v-erbB oncogene protein sequences. Nature 307,521 (1984)

    Article  PubMed  CAS  Google Scholar 

  49. J. A. Cooper, D. F. Bowen-Pope, E. Raines, R. Ross, T. Hunter, Similar effect of PDGF and epidermal growth factor on the phosphorylation of tyrosine in cellular proteins. Cell 31, 263 (1982)

    Article  PubMed  CAS  Google Scholar 

  50. T. Gilmore, J. Declue, G. S. Martin, Protein phosphorylation at tyrosine is induced by v-erb B gene product in vivo and in vitro. Cell 40,809 (1985)

    Article  Google Scholar 

  51. Y. J. Nishizuka, Turnover of inositol phospholipids and signal transduction. Science 223,1365 (1989)

    Google Scholar 

  52. M. J. Berridge, Inositol phosphates and cell signaling. Nature 341, 197 (1989)

    Article  PubMed  CAS  Google Scholar 

  53. T. Maniatis, S. Goodbourn, J. A. Fischer, Regulation of inducible and tissue-specific gene expression. Science 236,1237 (1987)

    Article  PubMed  CAS  Google Scholar 

  54. A. G. Gilman, Proteins and dual control of adenylate cyclase, Cell 36,577 (1984)

    Article  PubMed  CAS  Google Scholar 

  55. T. G. Powles, R. S. Bockman, K. V. Honn, “Prostaglandins and Cancer.” Alan Liss, N.Y. (1982)

    Google Scholar 

  56. L. Coussens, P. J. Parker, L. Rhee et al., Multiple distinct forms of bovine and human protein kinase C suggest diversity in cellular signaling pathways. Science 233,859 (1986)

    Article  PubMed  CAS  Google Scholar 

  57. Y. Nishizura, The role of protein kinase C in cell surface signal transduction and tumor formation. Nature 208,693 (1984)

    Article  Google Scholar 

  58. A. M. Jetten, B. R. Gaong, G. R. Vandenbark, J. E. Shirley, R. M. Bell, Role of protein kinase C in reduction of epidermal growth factor binding. Proc. Natl. Acad. Sci (USA) 82,1941 (1985)

    Article  CAS  Google Scholar 

  59. J. C. Fermi, A. C. King, EGF receptor affinity is regulated by intracellular calcium and protein kinase C. Cell 40,991 (1985)

    Article  Google Scholar 

  60. C. R. Lin, W. S. Chen, C. S. Lazar et al., Protein kinase C phosphorylation at thr.654 of the EGF-receptor and EGF binding regulate functional receptor loss by independent mechanisms. Cell 44,839 (1986)

    Article  PubMed  CAS  Google Scholar 

  61. T. Kamata, J. R. Feramisco, Epidermal growth factor stimulates guanine nucleotide binding activity and phosphorylation of ras oncogene proteins. Nature 310,147 (1984)

    Article  PubMed  CAS  Google Scholar 

  62. K. R. Yamamoto, Steroid receptor regulated transcription of specific genes and gene networks. Annu. Rev. Genet. 19,209 (1985)

    Article  PubMed  CAS  Google Scholar 

  63. S. Green, P. Chambon, A superfamily of potentially oncogenic hormone receptors. Nature 324,615 (1986)

    Article  PubMed  CAS  Google Scholar 

  64. D. T. Kanazir and R. Djordjevic-Markovic, Steroid hormones secretion and steroid receptor in carcinogenesis. In “Malignant Cell Secretion,” 1990 (V. Krsmanovic and J.F. Whitfield, Eds.) in press. CRC Press, Inc., Boca Raton

    Google Scholar 

  65. D. T. Kanazir, Glucocorticoid receptor and hormonal extragenomic effects. In “Activation of Hormone and Growth Factor Receptors, Molecular Mechanisms and Consequences,” 1990 (M.N. Alexis and C.E. Sekeris, Eds.) p.269. Kluwer Academic Publishers, Dordrecht, Boston

    Chapter  Google Scholar 

  66. D. T. Kanazir, The role of Steroid receptors in the regulation and integration of steroid and peptide hormone actions in common target cells. In “Hormonally Active Brain Peptides,” 1982 (W.K. McKerns and V. Pantic, Eds.) Chapter 10. Plenum Press, New York

    Google Scholar 

  67. C. Weinberger, V. Giquere, S. Hollengerg et al., Human steroid receptors and erb A protooncogene products: Members of a new superfamily of enhancer binding proteins. Cold Spring Harbor Symp. (1986)

    Google Scholar 

  68. C. Weiberger, C. C. Thompson, E. S. Ong et al., The c-erb A gene encodes a thyroid hormone receptor. Nature 324,641 (1986)

    Article  Google Scholar 

  69. C. Weinberger, S. M. Hollenberg, M. G. Rosenfeld, Domain structure of human, glucocorticoid receptor and its relationship to the v-erbA oncogene product. Nature 318,670 (1985)

    Article  PubMed  CAS  Google Scholar 

  70. P. Kahn, L. Frykberg, C. Brady et al., V-erb A cooperates with sarcoma oncogenes in leukemic cell transformation. Cell 45, 349 (1986)

    Article  PubMed  CAS  Google Scholar 

  71. T. Graf, M. Beng, Role of v-erb A and v-erb B oncogenes of avian erythroblastosis virus in eryrthroid cell transformation. Cell 34,7 (1983)

    Article  PubMed  CAS  Google Scholar 

  72. R. Djordjevic-Markovic, Structure of glucocorticoid receptor in cancer tissues. In “Activation of Hormone and Growth Factor Receptors, Molecular Mechanisms and Consequences,” 1990 (M.A. Alexis and C.E. Sekeris, Eds). Kluwer Academic Publishers, Dordrecht, Boston

    Google Scholar 

  73. C. H. Hennekens, Vitamin A analogues in cancer chemoprevention. In “Important Advances in Oncology,” 1986 (V.T. De Vita, S. Hellman and S.A. Rosenberg, Eds.) p.23. J.B.Lippincott, Philadelphia

    Google Scholar 

  74. M. S. Menkes, G. W. Comstock, J. P. Vuilleumier et al., Serum beta-carotene, vitamin A and E, selenium and the risk of lung cancer. N. Enzl, J. Med, 315,1250 (1986)

    Article  CAS  Google Scholar 

  75. E. C. Borden, Y. A. Sidky and G. T. Bryan, Chemoprophylaxis by interferons or inducers against chemical carcinogenesis. In “Anticarcinogenesis and Radiation Protection,” 1987 (P.A. Cerutti, O.F. Nygaard and M.G. Simic) p.499. Plenum Press, New York

    Chapter  Google Scholar 

  76. S. De Flora, Antimutagenic and anticarcinogenic mechanisms of aminothiols. (These proceedings.)

    Google Scholar 

  77. Y. Muto, Acyclic retinoids as anticarcinogens. In: “Abstracts, 3rd International Conference on Anticarcinogenesis and Radiation Protection,” Dubrovnik, Yugoslavia. 1989, p. 60

    Google Scholar 

  78. H. Fujiki, M. Suganuma, K. Takagi et al. Tumor antipromoters; Sarcophytols A and B, (-)-epigallocatechin gallate (EGCF) and morusin. (These proceedings.)

    Google Scholar 

  79. H. Koprowski, D. Herlyn, M. Lubeck et al., Human anti-idiotype antibodies in cancer patients; Is the modulation of the immune response beneficial for the patient? Proc. Natl. Acad. Sci. (USA) 81,216 (1984)

    Article  CAS  Google Scholar 

  80. R. Levy, P. Stratte, M. Link et al., Monoclonal antibodies to human lymphocytes: clinical application in therapy of leukemia. In “Monoclonal Antibodies and Functional Cell Line,” 1984 (R.H. Kennett, K.B. Bechtol, T.J. McKearn Eds), p.193. Plenum Press, New York

    Chapter  Google Scholar 

  81. J. A. Drebin, D. F. Stern, V. G. Link, Monoclonal antibodies identifying a cell-surface antigen associated with an activated cellular oncogene. Nature 312,545 (1984)

    Article  PubMed  CAS  Google Scholar 

  82. R. J. Cote, K. N. Houghton, The generation of human monoclonal antibodies and their use in the analysis of the humoral immune response to cancer. In “Human Hybridomas and Monoclonal Antibodies,” 1985 (E.G. Engleman, S.K.H. Foung, J.W. Larrick, A. Raubitschek, Eds.) p.189. Plenum Press, New York

    Chapter  Google Scholar 

  83. D. J. Fitzgerald, M. C. Willingham, I. Pastan, Antitumor effects of an immunotoxin made with Pseudomonas exotoxin in a nude mouse model of ovarian cancer. Proc. Natl. Acad. Sci. (USA) 83,6627 (1986)

    Article  CAS  Google Scholar 

  84. T. Lindao, E. Boven, J B. Mitchell et al. Specific killing of human melanoma cells by I-labeled monoclonal antibody, Cancer Res. 45,5080 (1985)

    Google Scholar 

  85. I. H. Maxwell, F. Maxwell, L. M. Clode, Regular expression of diphtheria toxin alpha-chain gene transfected into human cells: possible strategy for inducing cancer cell suicide. Cancer Res. 46,4660 (1986)

    PubMed  CAS  Google Scholar 

  86. L. M. Sullivan, J. P. Quigley, An anticatalytic monoclonal antibody to avian plasminogen activator: its effect on behavior of RSV-transformed chick fibroblasts. Cell 45,905 (1986)

    Article  PubMed  CAS  Google Scholar 

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  1. Serbian Academy of Sciences and Arts Department of Molecular Biology and Endocrinology, Institut “Boris Kidric”, Vinca, Belgrade, Yugoslavia

    D. T. Kanazir

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  1. Case Western Reserve University, Cleveland, Ohio, USA

    Oddvar F. Nygaard

  2. New York University Medical Center, New York, USA

    Arthur C. Upton

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Kanazir, D.T. (1991). Cancer - Facts, Dilemmas and Mysteries. In: Nygaard, O.F., Upton, A.C. (eds) Anticarcinogenesis and Radiation Protection 2. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3850-9_1

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