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Transforming Growth Factors Produced by Viral-Transformed and Human Tumor Cells

  • George J. Todaro
  • Hans Marquardt
  • Daniel R. Twardzik
  • Fred H. ReynoldsJr.
  • John R. Stephenson

Abstract

The isolation of retroviruses with acute transforming function has occurred with increasing frequency over the past few years. Such viruses represent genetic recombinants between host cellular sequences (oncogenes) and non-transforming type C virus structural genes (Fischinger, 1980; Klein, 1982). Viruses of this nature transform cells in culture and induce neoplasms of a variety of histological classes in vivo. Although the number of independent retrovirus isolates is high, the total number of unique “oncogenes” so far represented in such viruses is only 13 or 14 (Coffin et al., 1981). Several of these are represented as multiple virus isolates of the same oncogene, and in several instances have originated in different species (Weinberg, 1982). By comparison to transforming sequences identified within the DNA of in-vitro-propagated human tumor cells, one oncogene, c-has, has been implicated in the induction of human bladder carcinomas (Der et al., 1982; Parada et al., 1982; Santos et al., 1982), whereas a second gene, c-kis, appears to be associated with carcinomas of the lung (Der et al., 1982). Other cellular homologues of viral oncogenes including c-myc (Dalla-Favera et al., 1982), c-fes (Dalla-Favera et al., 1982; Heisterkamp et al., 1982), c-sis (Swan et al.,1982), and c-abl (Heisterkamp et al., 1982) have been mapped on chromosomes involved in translocations frequently associated with human lymphoid neoplasms.

Keywords

Epidermal Growth Factor Receptor Epidermal Growth Factor Human Tumor Cell Epidermal Growth Factor Binding Murine Sarcoma Virus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Anzano, M. A., Roberts, A. B., Meyers, C. A., Komoriya, A., Lamb, L. C, Smith, J. M., and Sporn, M. B., 1982, Synergistic interaction of two classes of transforming growth factors from murine sarcoma cells, Cancer Res. 42:4776–4778.PubMedGoogle Scholar
  2. Barbacid, M., Beemon, K., and Devare, S. G., 1980, Origin and functional properties of the major gene product of the Snyder-Theilen strain of feline sarcoma virus, Proc. Natl. Acad. Sci. USA 77:5158–5162.PubMedCrossRefGoogle Scholar
  3. Blomberg, J., Reynolds, F. H., Jr., Van de Ven, W. J. M., and Stephenson, J. R., 1980, Abelson murine leukaemia virus transformation involves loss of epidermal growth factor-binding sites, Nature 286:504–507.PubMedCrossRefGoogle Scholar
  4. Chang, E. H., Furth, M. E., Scolnick, E. M., and Lowy, D. R., 1982, Tumorigenic transformation of mammalian cells induced by a normal human gene homologous to the oncogene of Harvey murine sarcoma virus, Nature 297:479–483.PubMedCrossRefGoogle Scholar
  5. Coffin, J. M., Varmus, H. E., Bishop, J. M., Essex, M., Hardy, W. D., Jr., Martin, G. S., Rosenberg, N. E., Scolnick, E. M., Weinberg, R. A., and Vogt, P. K., 1981, Proposal for naming host cell-derived inserts in retrovirus genomes, J. Virol. 40:953–957.PubMedGoogle Scholar
  6. Dalla-Favera, R., Franchini, G., Martinotti, S., Wong-Staal, F., Gallo, R. C., and Croce, C. M., 1982, Chromosomal assignment of the human homologues of feline sarcoma virus and avian myeloblastosis virus onc genes, Proc. Nat. J. Acad. Sci. USA 79:4714–4717.CrossRefGoogle Scholar
  7. De Larco, J. E., and Todaro, G. J., 1978, Growth factors (SGFs) produced by murine sarcoma virus-transformed cells, Proc. Nat. J. Acad. Sci. USA 75:4001–4005.CrossRefGoogle Scholar
  8. De Larco, J. E., and Todaro, G. J., 1980, Sarcoma growth factor (SGF): Specific binding to epidermal growth factor (EGF) membrane receptors, J. Cell. Physiol. 102:267–277.PubMedCrossRefGoogle Scholar
  9. De Larco, J. E., Preston, Y. A., and Todaro, G. J., 1981, Properties of a sarcoma-growth factorlike peptide from cells transformed by a temperature-sensitive sarcoma virus, J. Cell. Physiol. 109:143–152.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 79:3637–3640.PubMedCrossRefGoogle Scholar
  11. Fischinger, P. J., 1980, Type C RNA transforming viruses, in: MolecularBiology of RNA TumorViruses (J. R. Stephenson, ed.), Academic Press, New York, pp. 163–198.Google Scholar
  12. Groffen, J., Heisterkamp, N., and Stephenson, J. R., 1983, Isolation of v-fms and its human cellular homolog, Virology 126:248–258.PubMedCrossRefGoogle Scholar
  13. Hampe, A., Laprevotte, I., Galibert, F., Fedele, L. A., and Sherr, C. J., 1982, Nucleotide sequences of feline retroviral oncogenes (v-fes) provide evidence for a family of tyrosine-specific protein kinase genes, Cell 30:775–785.PubMedCrossRefGoogle Scholar
  14. Heisterkamp, N., Groffen, J., Stephenson, J. R., Spurr, N. K., Goodfellow, P. N., Solomon, E., Carritt, B., and Bodmer, W. F., 1982, Chromosomal localization of human cellular homologues of two viral oncogenes, Nature 299:747–749.PubMedCrossRefGoogle Scholar
  15. Kitamura, N., Kitamura, A., Toyoshima, K., Hirayama, Y., and Yoshida, M., 1982, Avian sarcoma virus Y73 genome sequence and structural similarity of its transforming gene product to that of Rous sarcoma virus, Nature 297:205–208.PubMedCrossRefGoogle Scholar
  16. Klein, G. (ed.), 1982, Advances in Viral Oncology, Raven Press, New York.Google Scholar
  17. Marquardt, H., and Todaro, G. J., 1982, Human transforming growth factor: Production by a melanoma cell line, purification, and initial characterization, J. Biol.. Chem. 257:5220–5225.PubMedGoogle Scholar
  18. Marquardt, H., Hunkapiller, M. W., Hood, L. E., Twardzik, D. R., De Larco, J. E., Stephenson, J. R., and Todaro, G. J., 1983, Transforming growth factors produced by retrovirus-transformed fibroblasts and human melanoma cells: Amino acid sequence homology with epidermal growth factor, Proc. Natl. Acad. Sci. USA 80:4684–4688.PubMedCrossRefGoogle Scholar
  19. Massague, J., Czech, M. P., lwata, K., De Larco, J. E., and Todaro, G. J., 1982, Affinity labeling of a transforming growth factor receptor that does not interact with epidermal growth factor, Proc. Natl. Acad. Sci. USA 79:6822–6826.PubMedCrossRefGoogle Scholar
  20. Ozanne, B., Fulton, R. J., and Kaplan, P. L., 1980, Kirsten murine sarcoma virus transformed cell lines and a spontaneously transformed rat cell-line produce transforming growth factors, J. Cell. Physiol. 105:163–180.PubMedCrossRefGoogle Scholar
  21. Parada, L. F., Tabin, C. J., Shih, C, and Weinberg, R. A., 1982, Human EJ bladder carcinoma oncogene is homologue of Harvey sarcoma virus ras gene, Nature 297:474–478.PubMedCrossRefGoogle Scholar
  22. Pike, L. J., Gallo, B., Casnellie, J. E., Bornstein, P., and Krebs, E. G., 1982a, Epidermal growth factor stimulates the phosphorylation of synthetic tyrosine-containing peptides by A431 cell membranes, Proc. Natl. Acad. Sci. USA 79:1443–1447.PubMedCrossRefGoogle Scholar
  23. Pike, L. J., Marquardt, H., Todaro, G. J., Gallis, B., Casnellie, J. E., Bornstein, P., and Krebs, E. G., 1982b, Transforming growth factor and epidermal growth factor stimulate the phosphorylation of a synthetic, tyrosine-containing peptide in a similar manner, J. Biol. Chem. 257:14628–14634.PubMedGoogle Scholar
  24. Reynolds, F. H., Jr., Van de Ven, W. J. M., and Stephenson, J. R., 1980a, Abelson-murine leukemia virus transformation-defective mutants with impaired P120-associated protein kinase activity, J. Virol. 36:374–386.PubMedGoogle Scholar
  25. Reynolds, F. H., Jr., Van de Ven, W. J. M., and Stephenson, J. R., 1980b, Feline sarcoma virus P115-associated protein kinase phosphorylates tyrosine. Identification of a cellular substrate conserved during evolution, J. Biol. Chem. 255:11040–11047.PubMedGoogle Scholar
  26. Reynolds, F. H., Jr., Todaro, G. J., Fryling, C., and Stephenson, J. R., 1981a, Human transforming growth factors induce tyrosine phosphorylation of EGF receptors, Nature 292:259–262.PubMedCrossRefGoogle Scholar
  27. Reynolds, F. H., Jr., Van de Ven, W. J. M., Blomberg, J., and Stephenson, J. R., 1981b, Differences in mechanisms of transformation by independent feline sarcoma virus isolates, J. Virol. 38:1084–1089.PubMedGoogle Scholar
  28. Reynolds, F. H., Jr., Van de Ven, W. J. M., Blomberg, J., and Stephenson, J. R., 1981c, Involvement of a high-molecular-weight polyprotein translational product of Snyder-Theilen feline sarcoma virus in malignant transformation, J. Virol. 37:643–653.PubMedGoogle Scholar
  29. Sacks, T. L., Hershey, E. J., and Stephenson, J. R., 1979, Abelson murine leukemia virus-infected cell lines defective in transformation, Virology 97:231–240.PubMedCrossRefGoogle Scholar
  30. Santos, E., Tronick, S. R., Aaronson, S. A., Pulciani, S., and Barbacid, M., 1982, T24 human bladder carcinoma oncogene is an activated form of the normal human homologue of BALB-and Harvey-MSV transforming genes, Nature 298:343–347.PubMedCrossRefGoogle Scholar
  31. Savage, C. R., Jr., Hash, J. H., and Cohen, S., 1973, Epidermal growth factor. Location of disulfide bonds, J. Biol. Chem. 248:7669–7672.PubMedGoogle Scholar
  32. Shibuya, M., and Hanafusa, H., 1982, Nucleotide sequence of Fujinami sarcoma virus: Evolutionary relationship of its transforming gene with transforming genes of other sarcoma viruses, Cell 30:787–795.PubMedCrossRefGoogle Scholar
  33. Shih, T. Y., Papageorge, A. G., Stokes, P. E., Weeks, M. O., and Scolnick, E. M., 1980, Guanine nucleotide-binding and autophosphorylating activities associated with the p21 src of Harvey murine sarcoma virus, Nature 287:686–691.PubMedCrossRefGoogle Scholar
  34. Stephenson, J. R. (ed.), 1980, Molecular Biology of RNA Tumor Viruses, Academic Press, New York.Google Scholar
  35. Swan, D. C., McBride, O. W., Robbins, K. C., Keithley, D. A., Reddy, E. P., and Aaronson, S. A., 1982, Chromosomal mapping of the simian sarcoma virus onc gene analogue in human cells, Proc. Natl. Acad. Sci. USA 79:4691–4695.PubMedCrossRefGoogle Scholar
  36. Todaro, G. J., and De Larco, J. E., 1978, Growth factors produced by sarcoma virus transformed cells, Cancer Res. 38:4147–4154.PubMedGoogle Scholar
  37. Todaro, G. J., De Larco, J. E., and Cohen, S., 1976, Transformation by murine and feline sarcoma viruses specifically blocks binding of epidermal growth factor (EGF) to cells, Nature 264:26–31.PubMedCrossRefGoogle Scholar
  38. Todaro, G. J., Fryling, C., and De Larco, J. E., 1980, Transforming growth factors produced by certain human tumor cells: Polypeptides that interact with epidermal growth factor receptors, Proc. Natl. Acad. Sci. USA 77:5258–5262.PubMedCrossRefGoogle Scholar
  39. Todaro, G. J., Marquardt, H., De Larco, J. E., Reynolds, F. H., Jr., and Stephenson, J. R., 1981, Transforming growth factors produced by human tumor cells: Interactions with epidermal growth factor (EGF) membrane receptors, in: Cellular Responses to Molecular Modulators (W. Scott, R. Werner, and J. Schultz, eds.), Academic Press, New York, pp. 183–204.Google Scholar
  40. Twardzik, D. R., Todaro, G. J., Marquardt, H., Reynolds, F. H., Jr., and Stephenson, J. R., 1982, Transformation induced by Abelson murine leukemia virus involves production of a polypeptide growth factor, Science 216:894–897.PubMedCrossRefGoogle Scholar
  41. Twardzik, D. R., Todaro, G. J., Reynolds, F. H., Jr., and Stephenson, J. R., 1983, Similar transforming growth factors (TGFs) produced by cells transformed by different isolates of a feline sarcoma virus, Virology 124:201–207.PubMedCrossRefGoogle Scholar
  42. Ushiro, H., and Cohen, S., 1980, Identification of a phosphotyrosine as a product of epidermal growth factor-activated protein kinase in A-431 cell membranes, J. Biol. Chem. 255:8363–8365.PubMedGoogle Scholar
  43. Van de Ven, W. J. M., Reynolds, F. H., Jr., and Stephenson, J. R., 1980, The nonstructural components of polyproteins encoded by replication-defective mammalian transforming retroviruses are phosphorylated and have associated protein kinase activity, Virology 101:185–197.PubMedCrossRefGoogle Scholar
  44. Weinberg, R. A., 1982, Fewer and fewer oncogenes, Cell 30:3–4.PubMedCrossRefGoogle Scholar
  45. Witte, O. N., Dasgupta, A., and Baltimore, D., 1980, Abelson murine leukaemia virus protein is phosphorylated in vitro to form phosphotyrosine, Nature 283:826–831.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • George J. Todaro
    • 1
  • Hans Marquardt
    • 1
  • Daniel R. Twardzik
    • 1
  • Fred H. ReynoldsJr.
    • 1
  • John R. Stephenson
    • 1
  1. 1.Laboratory of Viral Carcinogenesis, National Cancer InstituteNational Institutes of HealthFrederickUSA

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