Retroviral Oncogenes and Human Neoplasia

  • E. Premkumar Reddy
Part of the Basic Life Sciences book series


Carcinogenesis is a complex multistep process. For a molecular biologist seeking simpler model systems to gain insight into this neoplastic process, retroviruses have provided an excellent system because of their relatively simple biochemical organization. These viruses fall into two major groups: chronic leukemia viruses and acute transforming viruses. Chronic leukemia viruses cause tumors in susceptible hosts but only after a prolonged latent period of several months. These viruses are replication competant and can be propagated in vitro without transforming their host cells. In contrast, acute transforming viruses induce a variety of tumors including sarcomas, carinomas and hematopoietic tumors with a short latent perod of days to weeks. These viruses are generally replication defective and induce transformation of appropriate assay cells in vitro. Because of these properties, acute transforming viruses have been the subject of intensive investigations in the past two decades which have led to several important insights into the mechanisms involved in carcinogenesis.


Transforming Gene Avian Myeloblastosis Virus Proviral Genome Human Neoplasia Bladder Carcinoma Cell Line 
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  1. Abelson, H.T., and Rabstein, L.S., 1970, Lymposarcoma: Virus induced thymic-independent disease in mice, Cancer Res., 3:2208.Google Scholar
  2. Anderson, P.R., Devare, S.G., Tronick, S.R., Ellis, R.W., Aaronson, S.A., and Scolnick, E.M., 1981, Generation of BALB-MUSV and HA-MUSV by type C virus transduction of homologous transforming genes from different species, Cell, 26:129.CrossRefGoogle Scholar
  3. Anderson, P.R., Tronick, S.R., and Aaronson, S.A., 1981a, Structural organization and biological activity of molecular clones of the integrated genome and BALB/c mouse sarcoma virus, J. Virol., 40:431.Google Scholar
  4. Baltimore, D., 1974, Tumor Viruses, Cold Spring Harbor Symp. Quant. Biol., 39:1187.CrossRefGoogle Scholar
  5. Baluda, M.A., and Goetz, I.E., 1961, Morphological conversion of cell cultures by avian myeloblastosis virus, Virology, 15:185PubMedCrossRefGoogle Scholar
  6. Boyle, W.J., Lipsick, J.S., Reddy, E.P., and Baluda, M.A., 1983, Identification of the leukemogenic protein of avian myeloblastosis virus and of its normal cellular homologue, Proc. Natl. Acad. Sci. USA, 80:2834.PubMedCrossRefGoogle Scholar
  7. Capon, D.J., Seeburg, P.H., McGratti, J.P., Hayflick, J.S., Edman, U., Levinson, A.D., and Goeddel, D.V., 1983, Activation of Kiras-2 gene in human colon and lung carcinomas by two different point mutations, Nature (London), 304:507.CrossRefGoogle Scholar
  8. Coffin, J., 1982, Structure of the retroviral genome, in: “RNA Tumor Viruses,” pp. 261–368, R. Weiss, N. Teich, H. Varmus, and J. Coffin, eds., Cold Spring Harbor Laboratory, New York.Google Scholar
  9. Cooper, G.M., 1982, Cellular transforming genes, Science, 217: 801.PubMedCrossRefGoogle Scholar
  10. Der, C.J., Krontiris, T.G., and Cooper, G.M., 1982, Transforming genes of human bladder and lung carcinoma cell lines are homologous to the ras genes of Harvey and Kirsten sarcoma viruses, Proc. Natl. Acad. Sci., USA, 79:3637.PubMedCrossRefGoogle Scholar
  11. Dhar, R., Ellis, R.W., Shih, T.Y., Oroszalan, S., Shapiro, B., Maizel, J., Lowy, D., and Scolnick, E., 1982, Nucleotide sequence of the p21 transforming protein of Harvey murine sarcoma virus, Science, 217:934.PubMedCrossRefGoogle Scholar
  12. Dhar, R., McClements, W.L., Enquist, L.W., and Van de Wonde, G.W., 1980, Nucleotide sequence of integrated Moloney sarcoma pro-virus long terminal repeats and their host and viral junctions, Proc. Natl. Acad. Sci USA, 77:3937.PubMedCrossRefGoogle Scholar
  13. Goff, S.P., Gilboa, E., Witte, O.N., and Baltimore, D., 1980, Structure of the Abelson murine leukemia virus genome and the homologous cellular gene: Studies with cloned viral DNA, Cell, 22:777.PubMedCrossRefGoogle Scholar
  14. Goldfarb, M., Shimizu, K., Perucho, M., and Wigler, M., 1982, Isolation and preliminary characterization of a human transforming gene from T24 bladder carcinoma cells, Nature (London), 296:404.CrossRefGoogle Scholar
  15. Graham, F.L., and Van der Eb, A.J., 1973, Transfection of rat cells by DNA of human adenovirus 5, Virology, 52:456.PubMedCrossRefGoogle Scholar
  16. Klempnauer, K.H., Ramsay, G., Bishop, J.M., Moscovici, M.G., Moscovici, C.J., McGrath, P., and Levinson, A.D., 1983, The product of the retroviral transforming gene v-myb is a truncated version of the protein encoded by the cellular oncogene c-myb, Cell, 33:345.PubMedCrossRefGoogle Scholar
  17. Kraus, M., Yuasa, Y., and Aaronson, S., 1984, A position 12 activated H-ras oncogene in all HS578T mammary carcinosarcoma cells but not normal mammary cells of the same patient, Proc. Natl. Natl. Acad. Sci. USA, 81:5384.CrossRefGoogle Scholar
  18. Nakano, H., Yamamoto, F., Neville, C., Evans, D., Mizano, T., and Perucho, M., 1984, Isolation of transforming sequences of two human lung carcinomas: Structural and functional analysis of the activated c-k-ras oncogenes, Proc. Natl. Acad. Sci. USA, 81:71.PubMedCrossRefGoogle Scholar
  19. Parada, L.F., Tabin, C.J., Shih, C., and Weinberg, R.A., 1982, Human EJ bladder carcinoma oncogene is a homologue of Harvey sarcoma virus ras gene, Nature (London), 297:474.CrossRefGoogle Scholar
  20. Peters, R.L., Rabstein, L.S., Louise, S., Van Vleck, R., Kelloff, G.J., and Huebner, R.J., 1974, Naturally occurring sarcoma virus of the BALB/c Cr mouse, J. Natl. Cancer Inst., 53:1725.PubMedGoogle Scholar
  21. Ponticelli, A.S., Whitlock, C.A., Rosenberg, N., and Witte, O.N., 1982, In vivo tyrosine phosphorylations of the Abelson virus transforming protein are absent in its normal cellular homolog, Cell, 29:953.PubMedCrossRefGoogle Scholar
  22. Premkumar, E., Potter, M., Singer, P.A., and Sklar, M.D., 1975, Synthesis, surface deposition, and secretion of immunoglobulins by Abelson virus transformed lymphosarcoma cell lines, Cell, 6:149.PubMedCrossRefGoogle Scholar
  23. Pulciani, S., Santos, E., Lauver, A.V., Long, L.K., Aaronson, S.A., and Barbacid, M., 1982a, Oncogenes in solid human tumors, Nature (London), 300:539.CrossRefGoogle Scholar
  24. Pulciani, S., Santos, E., Lauver, A.V., Long, L.K., Robbins, K.C., and Barbacid, M., 1982b, Oncogenes in human tumor cell lines: molecular cloning of a transforming gene from human bladder carcinoma cells, Proc. Natl. Acad. Sci. USA, 79:2845.PubMedCrossRefGoogle Scholar
  25. Reddy, E.P., 1983, Nucleotide sequence analysis of the T24 human bladder carcinoma oncogene, Science, 220:1061.PubMedCrossRefGoogle Scholar
  26. Reddy, E.P., Lipman, D., Anderson, P.R., Tronick, S.R., and Aaronson, S.A., 1985, Nucleotide sequence analysis of the BALB-MSV transforming gene, J. Virol., in press.Google Scholar
  27. Reddy, E.P., Reynolds, R.K., Santos, E., and Barbacid, M., 1982, A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene, Nature (London), 300:149.CrossRefGoogle Scholar
  28. Reddy, E.P., Smith, M.J., and Svinivasan, A., 1983, Nucleotide sequence of Abelson murine leukemia virus genome: Structural similarity of its transforming gene product to other one gene products with tyrosine-specific kinase activity, Proc. Natl. Acad. Sci. USA, 80:3623.PubMedCrossRefGoogle Scholar
  29. Rosenberg, N., and Baltimore, D., 1980, Abelson virus, in: “Viral Oncology,” pp. 187–203, G. Klein, ed., Raven, New York.Google Scholar
  30. Rushlow, K.E., Lautenberger, J.A., Papas, T.S., Baluda, M.A., Perbal, B.J., Chirikjian, G., and Reddy, E.P., 1982, Nucleotide sequence of the transforming gene of avian myeloblastosis virus, Science, 216, 1421.PubMedCrossRefGoogle Scholar
  31. Santos, E., Marin-Zanca, D., Reddy, E.P., Pierotti, M.A., Porta, G.D., and Barbacid, M., 1984, Malignant activation of a k-ras oncogene in lung carcinoma but not in normal tissue of the same patient, Science, 223:661.PubMedCrossRefGoogle Scholar
  32. Santos, E., Tronick, S.R., Aaronson, S.A., Puciani, S., and Barbacid, M., 1982, T24 human bladder carcinoma oncogene is an activated form of the normal homologue of BALB and Harvey-MSV transforming genes, Nature (London), 298:343.CrossRefGoogle Scholar
  33. Shih, C., and Weinberg, R.A., 1982, Isolation of a transforming sequence from a human bladder carcinoma cell line, Cell, 29:161.PubMedCrossRefGoogle Scholar
  34. Shimizu, K., Birnbaum, D., Ruley, M.A., Fasano, O., Suard, Y., Edland, L., Taparowsky, E., Goldfarb, M., and Wigler, M., 1983, Structure of Ki-ras gene of the human lung carcinoma cell line Calu-1, Nature (London), 304:496.CrossRefGoogle Scholar
  35. Souza, L.M., Strommer, J.N., Hillyard, R.L., Komaromy, M.C., and Baluda, M.A., 1980, Cellular sequences are present in the presumptive avian myeloblastosis virus genome, Proc. Natl. Acad. Sci. USA, 77:5177.PubMedCrossRefGoogle Scholar
  36. Shimotohono, K., Muzutani, S., and Temin, H.M., 1980, Sequence of retrovirus provirus resembles that of bacterial transposable elements, Nature (London), 285:550.CrossRefGoogle Scholar
  37. Tabin, C.J., Brodley, S.M., Bargmann, C.I., Weinberg, R.A., Papageorge, A.G., Scolnick, E.M., Dhar, R., Long, D.R., and Chang, E.H., 1982, Mechanism of activation of a human oncogene, Nature (London), 300:143.CrossRefGoogle Scholar
  38. Taparowsky, E., Shimizu, K., Goldfarb, M., and Wiegler, M., 1983, Structure and activation of the human N-ras gene, Cell, 34:581.PubMedCrossRefGoogle Scholar
  39. Tsuchida, N., Ryder, T., and Ohtubo, E., 1982, Nucleotide sequence of the oncogene encoding the p21 transforming protein of Kirsten murine sarcoma virus, Science, 217:937.PubMedCrossRefGoogle Scholar
  40. Wang, J.Y.J., and Baltimore, D., 1983, Cellular RNA homologous to the Abelson murine leukemia virus transforming gene: Expression and relationship to the viral sequence, Mol. Cell. Biol., 3:773.PubMedGoogle Scholar
  41. Wang, J.Y.J., Ledley, F., Goff, S., Lee, R., Grone, Y., and Baltimore, D., 1984, The mouse c-abl locus: Molecular cloning and characterization, Cell, 36:349.PubMedCrossRefGoogle Scholar
  42. Yuasa, Y., Srivastava, S.K., Dunn, C.Y., Rhim, J.S., Reddy, E.P., and Aaronson, S.A., 1983, Acquisition of transforming properties by alternative point mutations within c-bas/has human protooncogene, Nature (London), 303:775.CrossRefGoogle Scholar
  43. Yuasa, Y., Gol, R.A., Chang, A., Chiu, I., Reddy, E.P., Tronick, S.R., and Aaronson, S.A., 1984, Mechanism of activation of an N-ras oncogene of SW-1271 human lung carcinoma cells, Proc. Natl. Acad. Sci. USA, 81:3670.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • E. Premkumar Reddy
    • 1
  1. 1.Laboratory of Cellular and Molecular BiologyNational Cancer InstituteBethesdaUSA

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