Summary
The transformation of a normal into a tumor cell is not caused by a single molecular event, but is the consequence of several simultaneous or consecutive molecular processes, which lead to a variety of changes in the structure and the metabolism of the cell. Investigations with the Rous sarcoma virus show that a single gene is primarily responsible for these changes that is coding for a phosphorprotein which, however, is multifunctional. The biochemical and biologic events which initiate and maintain the transformed status of the cell involve mainly the cytoplasma membrane. At both the outer and the inner surface of the cell membrane dramatic changes occur which influence the cell structure, permeability of the cytoplasma membrane, and the intracellular metabolic pathways. Most probably, these transformation-associated events are also involved in cell proliferation under physiologic conditions. In the tumor cell, however, they are not further regulated physiologically, with the consequence of an uncontrolled and incessant cell division.
Zusammenfassung
Die Umwandlung einer normalen Zelle in eine Tumorzelle erfolgt nicht aufgrund eines einzigen molekularen Ereignisses. Sie ist vielmehr die Folge mehrerer gleichzeitiger oder aufeinanderfolgender molekularer Prozesse, die zahlreiche Veränderungen der Struktur und des Stoffwechsels der Zelle bewirken. Untersuchungen am Rous-Sarkom-Virus zeigen, daß hierfür primär ein einziges Gen verantwortlich ist, dessen Produkt, ein Phosphorprotein, aber offensichtlich mehrere Funktionen hat. Die biochemischen und biologischen Vorgänge, die zur Auslösung wie auch zur Aufrechterhaltung des Transformationsstatus der Zelle führen, spielen sich vor allem an der Zellmembran ab. Auf der äußeren wie auf der inneren Oberfläche der Zellmembran finden dramatische Veränderungen statt, welche die Zellstruktur, die Permeabilität der Zellmembran und die intrazellulären Wechselwirkungen betreffen. Dabei handelt es sich um Vorgänge, die sich vermutlich auch bei der physiologischen Zellteilung abspielen, deren physiologische Regulation aber in der Tumorzelle aufgehoben ist, was eine unkontrollierte und unaufhörliche Zellteilung zur Folge hat.
Vortrag auf der 111. Versammlung der Gesellschaft Deutscher Naturforscher und Ärzte, Hamburg, 21.–25. September 1980
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Literatur
Balk SD, Polimeni PI, Hoon BS, LeStourgeon DN, Mitchell RS (1979) Proliferation of Rous sarcoma virus-infected, but not of normal chicken fibroblasts in a medium of reduced Ca and Mg concentration. Proc Natl Acad Sci USA 76: 3913–3916
Barnekow A, Bauer H, Boschek CB, Friis RR, Ziemiecki A (1981) Rous sarcoma virus transformation: action of the src gene product. In: Schweiger NG (ed) Cell biology. Springer, Berlin Heidelberg New York, pp 457–466
Bauer H, Hayami M, Ignjatovic J, Rübsamen H, Graf T, Friis RR (1978) On the origin and in vivo immunogenicity of avian sarcoma cell surface antigens. In: Barlaty S, Guili-Morghen C de (eds) Avian RNA tumor viruses. Piccin, Medical Books, pp 252–267
Bauer H, Yoshikawa Y (1980) Oncofetal antigens as markers for retrodifferentiation in malignant transformation. In: Viruses in naturally occuring cancers, Cold Spring harbor conferences on cell proliferation. Cold Spring Harbor Laborator, (Vol 7, pp 1231–1238 )
Boschek CB, Jockusch BM, Friis RR, Back R, Grundmann E, Bauer H (1981) Early changes in the distribution and organization of microfilament proteins during cell transformation. Cell 24: 175–184
Brugge JS, Erikson RL (1977) Identification of a transformation-specific antigen induced by an avian sarcoma virus. Nature 269: 346–348
Brugge JS, Collett MS, Siddiqui A, Marczynska B, Deinhardt F, Erikson RL (1979) Detection of the viral sarcoma gene product in cells infected with various strains of avian sarcoma virus and of a related protein in infected chicken cells. J Virol 29: 1196–1203
Courtneidge SA, Levinson AD, Bishop JM (1980) The protein virus and of a related protein in infected chicken cells. J Virol 29: 1196–12 3
Courtneidge SA, Levinson AD, Biship JM (1980) The protein encoded by the transforming gene of avian sarcoma virus (pp60“`) and a homologous protein in normal cells (pp60 protosrc) are associated with the plasma membrane. Proc Natl Acad Sci USA 77: 3783–3787
Erikson E, Collett MS, Erikson RL (1978) In vitro synthesis of a functional avian sarcoma virus transforming-gene product. Nature 274: 919–921
Erikson RL, Collett MS, Erikson E, Purchio AF (1979) Evidence that the avian sarcoma virus transforming gene product is a cAMP-independent protein kinase. Proc Natl Acad Sci USA 76: 6260–6264
Friis RR, Schwartz RT, Schmidt MFG (1977) Phenotypes of Rous sarcoma virus transformed fibroblasts: an argument for a multifunctional src gene product. Med Microbiol Immunol 164: 155–165
Friis RR (1978) Temperature-sensitive mutants of avian RNA tumor viruses. A review. Curr Top Microbiol 79: 262–293
Glenney JR jr, Weber K (1980) Calmodulin-binding proteine of the microfilaments present in isolated brush borders and microvilli of intestinal epithelial cells. J Biol Chem 255: 10551–10554
Hunter T, Sefton BM (1980) Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. Proc Natl Acad Sci USA 77: 1311–1315
Hynes RO, Destree AT, Perkins ME, Wagner DD (1979) Cell surface fibronetin and oncogenic transformation. J Supramol Strut 11: 95–104
Ignjatovic J, Rübsamen H, Hayami M, Bauer H (1978) Rous sarcoma virus-transformed avian cells express four different cell surface antigens that are distinguishable by a cell-mediated cytotoxicity blocking test. J Immunol 120: 1663–1668
Laporte DC, Gidwitz S, Weber JM, Storm DR (1979) Relationship between changes in the calcium-dependent regulartory protein and adenylate cyclase during viral transformation. Biophys Res Commun 86: 1169–1177
Levinson AD, Oppermann H, Levintow L, Varmus HE, Bishop JM (1978) Evidence that the transforming gene of avian sarcoma virus encodes a protein kinase associated with a phosphoprotein. Cell 15: 561–572
Nicholson GL (1976) Transmembrane control of the receptors on normal and tumor cells. II. Surface changes associated with transformation and malignancy. Biophys Acta 458: 1–72
Presek P, Glossmann H, Eigenbrodt E, Schoner W, Rübsamen H, Friis RR, Bauer H (1980) Similarities between a phosphor-protein (pp60s) associated protein kinase of Rous sarcoma virus and a cyclic adenosine 3′: 5′-monophosphate-independent protein kinase that phosphorylates pyruvate kinase type M2. Cancer Res 40: 1733–1741
Radke K, Gilmore T, Martin GS (1980) Transformation by Rous sarcoma virus: a cellular substrate for transformation-specific protein phosphorylation contains phosphotyrosine. Cell 21: 821–828
Rozengurth E (1979) Early events in growth stimulation. In: Hynes RO (ed) Surfaces of normal and malignant cell. John Wiley zhaohuan Sons, Chichester New York Brisbane Toronto, pp 323–354
Rübsamen H, Friis RR, Bauer H (1979) The src gene product from different strains of avian sarcoma virus: Kinetics and possible mechanism of heat-inactivation of protein kinase activity from transformation defective temperature sensitive mutant-and wild-type virus-infected cells. Proc Natl Acad Sci USA 76: 967–971
Todaro GJ, Larco JE de (1978) Growth factors produced by sarcoma virus-transformed cells. Cancer Res 38: 4147–4153
Unkeless JC, Tobia A, Ossowski L, Quigley JP, Rifkin DB, Reich E (1973) An enzymatic function associated with transformation of fibroblasts by oncogenic viruses. I. Chick embryo fibroblast cultures transformed by avian RNA tumor viruses. J Exp Med 137: 85–111
Wang LH, Snyder P, Hanafusa T, Hanafusa H (1980) Evidence for the common origin of viral and cellular sequences involved in sarcomagenic transformation. J Virol 35: 52–64
Weber JM (1973) Hexose transport in normal and in Rous sarcoma virus-transformed cells. J Biol Chem 248: 2978–2983
Willingham MC, Jay G, Pastan I (1979) Localization of the ASV src gene product to the plasma membrane of transformed cells by electron microscopic immunocytochemistry. Cell 18: 125–134
Yoshikawa Y, Ignjatovic J, Bauer H (1979) Tissue-specific expression of onco-fetal antigens during embryogenesis. Differentiation 15: 41–47
Ziemiecki A, Friis RR (1980) Phosphorylation of pp60“`-associated kinase activity of transformation-defective temperature-sensitive mutants of Rous sarcoma virus. Virology 106: 391–394
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Bauer, H. (1981). Zellmembranveränderungen und biologisches Verhalten von Virus-transformierten Zellen. In: Verhandlungen der Gesellschaft Deutscher Naturforscher und Ärzte. Verhandlungen der Gesellschaft deutscher Naturforscher und Ärzte, vol 111. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-37791-8_25
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