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Wenn ein Gen fehlt — Die Rolle der Tumorsuppressorgene bei der Krebsentstehung

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Part of the book series: Heidelberger Jahrbücher ((HJB,volume 38))

Zusammenfassung

In den letzten Jahren konnte eine bemerkenswerte Übereinstimmung zwischen genetischen Daten und experimentell erarbeiteten Ergebnissen beobachtet werden, die zur Identifizierung und zum Verständnis der mit Krebsentstehung verbundenen genetischen Veränderungen führten. Diese Fortschritte eröffneten aufregende Einblicke in die Schaltmechanismen, die für die Umformung einer normalen Zelle in maligne wachsende Zellen verantwortlich sind.

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Literatur

  • Anders, E 1967. Tumour formation in platyfish-swordtail hybrids as a problem of gene regulation. Experimentia 23: 1–10.

    Article  Google Scholar 

  • Benedict, W.F., Murphree, A.L., Banerjee, A., Spina, C.A., Sparkes, M.C., and Sparkes, R.S. 1983. Patient with 13 chromosome deletion: evidence that the retinoblastoma gene is a recessive cancer gene. Science 219: 973–975.

    Article  Google Scholar 

  • Boedigheimer, M., and Laughon, A. 1993. expanded: a gene involved in the control of cell proliferation in imaginal discs. Development 118:1291–1301.

    Google Scholar 

  • Bridges, C.B., and Brehme, K.F. 1944. The mutation of Drosophila melanogaster. Carnegie Institute of Washington. Publication No. 552.

    Google Scholar 

  • Bryant, P.J., and Woods, D.F. 1992. A major palmitoylated membrane protein of human erythrocytes shows homology to yeast guanylate kinase and to the product of a Drosophila tumour gene. Cell 68: 621–622.

    Article  Google Scholar 

  • Buchkovich, K., Duffy, L.A., and Harlow, E. 1989. The retinoblastoma protein is phosphorylated during specific phases of the cell cycle. Cell 58: 1097–1105.

    Article  Google Scholar 

  • Cavenee, W.K., Dryja, T.P., Phillips, R.A., Benedict, W.F., Godbout, R., Gallie, B.L., Murphree, A.L., Strong, L., and White, R.L. 1983. Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature 305: 779–784.

    Article  Google Scholar 

  • Clark, A.R., Maandag, E.R., Van Roon, M., Van der Lugt, N.M.T., Van der Valk, M., Hooper, M.L., Berns, A., and Te Riele, H. 1992. Requirement for a functional Rb-1 gene in murine development. Nature 359: 328–330.

    Article  Google Scholar 

  • De Caprio, J.A., Ludlow, J.W., Lynch, D., Furukawa, Y., Griffin, J., Piwnica-Worms, H., Huang, C-M., and Livingston D.M. 1989. The product of the retinoblastoma susceptibility gene has properties of a cell cycle regulatory element. Cell 58: 1085–1095.

    Article  Google Scholar 

  • Dryja, T.P., Rapaport, J.M., Joyce, J.M., and Petersen, R.A. 1989. Molecular detection of deletion involving bang q14 of chromosome 13 in retinoblastomas. Proc.Natl.Acad.Sci. USA 83: 7391–7396.

    Article  Google Scholar 

  • Fearon, E.R., Cho, K.R., Nigro, J.M., Kern, S.E., Simons, J.W., Ruppert, J.M., Hamilton, S.R., Preisinger, A.C., Thomas, G., Kinzler, K.W., and Vogelstein, B. 1990. Identification of a chromosome 18q gene that is altered in colorectal cancers. Science 247: 49–56.

    Article  Google Scholar 

  • Finlay, C.A., Hinds, P.W., and Levine, A.J. 1989. The p53 proto-oncogene can act as a suppressor of transformation. Cell 57: 1083–1093.

    Article  Google Scholar 

  • Friend, S.H., Bernards, R., Rogeli, S., Weinberg, R.A., Rapopot, J.M., Albert, D.M., and Dryja, T.P. 1986. A human DNA segment with properties of the gene that predispose to retinoblastoma and osteosarcoma. Nature 323: 643–646.

    Article  Google Scholar 

  • Fung, Y.-K.T., Murphree, A.L., T’Ang, A., Qian, J., Hinriches, S.H., and Benedict, W.F. 1987. Structural evidence for the authenticity of the human retinoblastoma gene. Science 236: 1657–1661.

    Article  Google Scholar 

  • Gateff, E. 1978. Malignant neoplasms of genetic origin in the fruitfly Drosophila melanogaster. Science 200: 1446–1459.

    Article  Google Scholar 

  • Gateff, E., and Mechler, B.M. 1989. Tumor-suppressor genes of Drosophila melanogaster. CRC Crit. Rev. Oncogenesis 1: 221–245.

    Google Scholar 

  • Gateff, E., and Schneiderman, H.A. 1967. Developmental studies of a new mutation of Drosophila melanogaster: lethal malignant brain tumor l(2)gl4. American Zoologist 7: 760.

    Google Scholar 

  • Gateff, E., and Schneiderman, H.A. 1969. Neoplasms in mutant and cultured wild-type tissues of Drosophila. National Cancer Institute Monograph 31: 365–397.

    Google Scholar 

  • Gateff, E., and Schneiderman, H.A. 1974. Developmental capacities of benign and malignant neoplasms of Drosophila. Wilhelm Roux ’ Archiv for Entwicklung und Organogenese 176: 23–65.

    Article  Google Scholar 

  • Golubovsky, M.D. 1980. Mutational process and microevolution. Genetica 52 /53: 139–149.

    Google Scholar 

  • Green, M.M., and Sheperd, S.H.Y. 1979. Genetic instability in Drosophila melanogaster: the induction of specific chromosome 2 deletions by MR element. Genetics 92: 823–832.

    Google Scholar 

  • Hadorn, E. 1937. An accelerating effect of normal „ring glands“ on puparium formation in lethal larvae of Drosophila melanogaster. Proc.Nat.Acad.Sci.USA 23: 478–484.

    Article  Google Scholar 

  • Hadorn, E. 1955. Letalfaktoren in ihrer Bedeutung für Erbpathologie und Genphysiologie der Entwicklung. Georg Thieme Verlag, Stuttgart.

    Google Scholar 

  • Harris, C.C. 1993. p53: At the crossroads of molecular carcinogenesis and risk assessment. Science 262: 1980–1981.

    Article  Google Scholar 

  • Harris, H., Miller, O.J., Klein, G., Worst, P., and Tachibana, T., 1969. Suppression of malignancy by cell fusion. Nature 223: 363–368.

    Article  Google Scholar 

  • Hong, F.D., Huang, H-S., To, H., Young, L.-J.S., Oro, A., Bookstein, R., Lee, E. Y.-H.P. and Lee, W.-H. 1989. Structure of the human retinoblastoma gene. Proc.Natl.Acad.Sci. USA 86: 5502–5506.

    Article  Google Scholar 

  • Huang, H.J., Yee, J.-K., Shew, J.-Y. et al. (1988) Suppression of the neoplastic phenotype by replacement of the Rb gene in human cancer cells. Science 242: 1563–1566.

    Article  Google Scholar 

  • Jacks, T., Fazeli, A., Schmitt, E.M., Bronson, R.T., Godell, M.A., Weinberg, R.A. 1992. Effects of an RB mutation in the mouse. Nature 359: 288–294.

    Article  Google Scholar 

  • Jacob, L., Opper, M., Metzroth, B., Phannavong, B., and Mechler, B.M. 1987. Structure of the l(2)gl gene of Drosophila and delimitation of its tumor suppressor domain. Cell 50: 215–225.

    Article  Google Scholar 

  • Jenkins, J.R., Rudge, K., and Currie, G.A. 1984. Cellular immortalization by cDNA clone encoding the transformation-associated phosphoprotein p53. Nature 312: 651–654.

    Article  Google Scholar 

  • Karlson, P., and Hauser, G. 1952. Über die Wirkung des Puparisierungshormons bei der Wildform and der Mutante lgl von Drosophila. Zeitschrift für Naturforschung 7b: 80–83.

    Google Scholar 

  • Kastan, M.B., Onyekwere, O., Sidransky, D., Vogelstein, B., and Craig, R.W. 1991. Participation of p53 protein in the cellular response to DNA damage. Cancer Res. 51: 6304–6311.

    Google Scholar 

  • Kastan, M.B., Zhan, Q., El-Deity, W.S., Carrier, F., Jacks, T., Walsh, W.V., Plunkett, B.S., Vogelstein, B., and Fornace, A.J., Jr. 1992. A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell 71: 587–597.

    Article  Google Scholar 

  • Knudson, G.A. 1971. Mutation and cancer: Statistical study of retinoblastoma. Proc.Natl.Acad.Sci. USA 68: 820–823.

    Article  Google Scholar 

  • Knudson, G.A. 1993. All in the cancer family. Nature genetics 5: 103–104.

    Article  Google Scholar 

  • Knudson, G.A., and Strong, L.C. 1972. Mutation and cancer: a model for Wilms’ tumor of the kidney. J.Natl.Cancer Inst. 48: 313–324.

    Google Scholar 

  • Kuerbitz, S.J., Plunkett, B.S., Walsh, W.V., and Kastan, M.B. 1992. Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Proc.Natl.Acad.Sci. USA 89: 7491–7495.

    Article  Google Scholar 

  • Lane, D.P. 1992. Guardian of the Genome. Nature 358: 15–16.

    Article  Google Scholar 

  • Lane, D.P., and Crawford, L.V. 1979. T antigen is bound to a host protein in SV40-transformed cells. Nature 278: 261–263.

    Article  Google Scholar 

  • Lalande, M., Dryja, T.P., Schreck, R.R., Shipley, J., Flint, A., and Latt, S.A. 1984. Isolation of human chromosome 13-specific DNA sequences cloned from sorted chromosomal and potentially linked to the retinoblastoma locus. Cancer Genet. and Cytogenet. 13: 283–295.

    Article  Google Scholar 

  • Lee E.Y.P., Chang, C.Y., Hu, N., Wang, Y.J., Lai, C.C., Herrup, K., Lee, W.H., and Bradley, A. 1992. Mice deficient for Rb are nonviable and show defects in neurogenesis and hematopoiesis. Nature 359: 288–294.

    Article  Google Scholar 

  • Lee, W.-H., Bookstein, R., Hong, E, Young, L.-J., Shew, J.-Y., and Lee, E.Y.P. 1987. Human retinoblastoma susceptibility gene: cloning, identification, and sequence. Science 235: 1394–1399.

    Article  Google Scholar 

  • Lewis, E.B. 1945. The relation of repeats to position effect in Drosophila melanogaster. Genetics 36: 137–166.

    Google Scholar 

  • Li, F.P. 1988. Cancer families: human models of susceptibility to neoplasia. Cancer Res. 48: 5381–5386.

    Google Scholar 

  • Li, F.P. Fraumeni, J.F., Mulvihill, J.J. et al. 1988. A cancer family syndrome in twenty-four kindreds. Cancer Res. 48: 5358–5362.

    Google Scholar 

  • Linzer, D.I.H., and Levine, A.J. 1979. Characterization of a 54K dalton cellular SV40 tumor antigen in SV40 transformed cells. Cell 17: 43–52.

    Article  Google Scholar 

  • Ludlow, J.W., Shon, J., Pipas, J.M., Livingstone, D.M., and De Caprio, A. 1990. The retinoblastoma susceptibility gene product undergoes cell cycle-dependent dephosphorylation and binding to and release from SV40 large T. Cell 60: 387–396.

    Article  Google Scholar 

  • Mahoney, P.A., Weber, U., Onofrechuck, P., Biessmann, H., Bryant, P.J., and Goodman, C.S. 1991. The fat tumor suppressor gene in Drosophila encodes a novel member of the cadherin gene family. Cell 67: 853–868.

    Article  Google Scholar 

  • Malkin, D., Li, F.P., Strong, L.C. et al. 1990. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250: 1233–1238.

    Article  Google Scholar 

  • McGee, T.L., Yandell, D.W., and Dryja, T.P. 1989. Structure and partial genomic sequence of the human retinoblastoma susceptibility gene product. Gene 80: 119–128.

    Article  Google Scholar 

  • Mechler, B.M. 1984. Molecular cloning of the recessive oncogene lethal(2)giant larvae of Drosophila melanogaster. Europ.J. of Cell Biol. 33: 23.

    Google Scholar 

  • Mechler, B.M., McGinnis, W., and Gehring, W.J. 1985. Molecular cloning of lethal(2)giant larvae, a recessive oncogene of Drosophila melanogaster. EMBO J. 4: 1551–1557.

    Google Scholar 

  • Mechler, B.M., and Strand, D. 1990. Tumor suppression in Drosophila. In Tumor Suppressor Genes. pp 123–144 (ed. G. Klein) Marcel Dekker, Inc. New York and Basel.

    Google Scholar 

  • Merz, R., Schmidt, M., Török, I., Protin, U., Schuler, G., Walther, H.-R, Krieg, E, Gross, M., Strand, D., and B.M. Mechler (1990) Molecular action of the l(2)gl tumor suppressor gene of Drosophila melanogaster. 88: 163–167.

    Google Scholar 

  • Mittnacht, S., and Weinberg, R.A. 1991. G1/S phosphorylation of the retinoblastoma protein is associated with an altered affinity for the nuclear compartment. Cell 65: 381–393.

    Article  Google Scholar 

  • Opper, M., Schuler, G., and Mechler, B.M. 1987. Hereditary suppression of lethal(2)giant larvae malignant tumor development in Drosophila by gene transfer. Oncogene 1: 91–96.

    Google Scholar 

  • Oren, M., Maltzman, W., and Levine, A.J. 1981. Post-translational regulation of the 54K cellular tumor antigen in normal and transformed cells. Molecular and Cellular Biology 1: 101–110.

    Google Scholar 

  • Parada, L.F., Land, H., Weinberg, R.A., Wolf, D., and Rotter, V. 1984. Cooperation between gene encoding p53 tumour antigen and ras in cellular transformation. Nature 312: 649–651.

    Article  Google Scholar 

  • Rouleau, G.A., Merel, P., Lutchman, M., Sanson, M., Zucman, J., Marineau, C., Hoang-Xuan, K., Demczuk, S., Desmaze, C., Plougastel, B., Pulst, S.M., Lenoir, G., Bijlsma, E., Fashold, R., Dumanski, J., de Jong, P., Parry, D., Eldrige, R., Aurias, A., Delattre, O., and Thomas, G. 1993. Alteration in a new gene encoding a putative membrane-organizing protein causes neurofibromatosis type 2. Nature (Lond.) 363: 515–521.

    Article  Google Scholar 

  • Saxon, P.J., Srivatsan, E.S., and Stanbridge, E.J. 1986. Introduction of human chromosome 11 via microcell transfer controls tumorigenic expression of HeLa cells. EMBO J. 15: 3461–3466.

    Google Scholar 

  • Srivastava, S., Zou, Z., Pirollo, K., Blattner, W., and Chang, E.H. 1990. Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. Nature 348: 747–749.

    Article  Google Scholar 

  • Stanbridge, E.J. 1976. Suppression of malignancy in human cells. Nature 260: 17–20.

    Article  Google Scholar 

  • Stanbridge, E.J. 1992. Functional evidence for human tumour supppressor genes: chromosome and molecular studies. Cancer Surveys 12: 5–24.

    Google Scholar 

  • Stanius, R., Mafune, K., Lu, M., Chen, L., and Steele, G., Jr. 1990. Increased expression of ribosomal protein S6 in human colon cancer. Surg. Forum 41: 457–459.

    Google Scholar 

  • Stewart, M.J., and Denell, R. 1993. Mutations in the 5’ region of the Drosophila gene encoding ribosomal protein S6 are associated with tissue overgrowth. Mol. Cell. Biol. 13:2524–2535.

    Google Scholar 

  • T’Ang, A., Varley, J.M., Chakraborty, S., Murphree, A.L., and Fung, Y.-K.T. 1988. Structural rearrangement of the retinoblastoma gene in human breast carcinoma. Science 242: 263–266.

    Article  Google Scholar 

  • Toguchida, J., McGee, T.L., Paterson, J.C., Eagle, J.R., Tucker, S., Yandell, D.W., and Dryja, T.P. 1993. Complete genomic sequence of the human retinoblastoma susceptibility gene. Genomics 17: 535–543.

    Article  Google Scholar 

  • Tomotsune, D., Shoji, H., Wakamatsu, Y., Kondoh, H., and Takahashi, N. 1993. A mouse homologue of the Drosophila tumour-suppressor gene l(2)gl controlled by Hox-C8 in vivo. Nature 365: 69–872.

    Article  Google Scholar 

  • Török, T., Tick, G., Alvarado, M., and Kiss, I. 1993. P-lacW insertional mutagenesis on the second chromosome of Drosophila melanogaster: Isolation of lethal with different overgrowth phenotypes. Genetics 135: 71–80.

    Google Scholar 

  • Trofatter, J.A., MacCollin, M.M., Rutter, J.L., Murrell, J.R., Duyao, M.P., Parry, D.M., Eldridge, R., Kley, N., Menon, A.G., Pulaski, K., Haase, V.H., Ambrose, C.M., Munroe, D., Bove, C., Haines, J.L., Martuza, R.L., MacDonald, M.E., Seizinger, B.R., Short, M.P., Buckler, A.J., and Gusella, J.F. 1993. A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell 72: 791–800.

    Article  Google Scholar 

  • Tsukita, S., Itoh, M., Nagafuchi, A., Yonemura, S. and Tsukita, S. 1993. Submembranous junctional plaque proteins include potential tumor suppressor molecules. J. Cell Biology 123: 1049–1053.

    Article  Google Scholar 

  • Vogt, M. 1947. Verhalten transplantierter Ringdriisen „letaler“ Drosophila Larven. Zschr. Naturforsch. 2b: 292–294.

    Google Scholar 

  • Watson, K.L., Johnson, T.K., and Denell, R.B. 1991. Lethal(1)aberrant immune response mutations leading to melanotic tumor formation in Drosophila melanogaster. Devel. Genetics 12: 173–187.

    Article  Google Scholar 

  • Watson, K.L., Konrad, D.K., Woods, D.F., and Bryant, P.J. 1992. The Drosophila homolog of the human S6 ribosomal protein is required for tumor suppression in the haematopoietic system. Proc.Nat.Acad.Sci. USA 89:11302–11306.

    Article  Google Scholar 

  • Woods, D.F., and Bryant, P.J. 1991. The discs-large tumor suppressor gene of Drosophila encodes a guanylate kinase homolog localized at septate junctions. Cell 66: 451–464.

    Article  Google Scholar 

  • Yunis, J.J., and Ramsey, N. 1978. Retinoblastoma and sub-band deletion of chromosome 13. American Journal of Diseases of Children. 132: 161–163.

    Google Scholar 

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Mechler, B.M. (1994). Wenn ein Gen fehlt — Die Rolle der Tumorsuppressorgene bei der Krebsentstehung. In: Heidelberger Jahrbücher. Heidelberger Jahrbücher, vol 38. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79348-6_5

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  • DOI: https://doi.org/10.1007/978-3-642-79348-6_5

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