Skip to main content
Log in

Oncogene-related growth factors and growth factor receptors in human malignant glioma-derived cell lines

  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Oncogenes induce malignant transformation of cells. Two oncogenes are closely related to genes coding for a mitogenic growth factor (v-sis to the PDGF gene) and a receptor for a mitogenic growth factor (v-erb B to the EGF receptor gene). We studied the possibility that cells derived from malignant gliomas produce mitogenic factors that bind to cell surface receptors, the activation of which could lead to excessive stimulation of cell proliferation. All six cell lines tested secrete into their medium factors that stimulate DNA synthesis. The factor secreted by one cell line was characterized and found to resemble PDGR Six of 11 cell lines had receptors for PDGF demonstrable by binding and receptor autophosphorylation assays. Six of six cell lines tested had EGF receptors demonstrable by binding and receptor autophosphorylation experiments. The extremely high levels of EGF receptor in one cell line may reflect excessive expression of the erb B oncogene associated with abnormalities of chromosome 7 that occur in this cell line.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Heldin CH, Wasteson A, Westermark B: Platelet-derived growth factor. Mol Cell Endocrinol 39:169–187, 1985

    Google Scholar 

  2. O'Keefe EJ, Pledger WJ: A model of cell cycle control: Sequential events regulated by growth factors. Mol Cell Endocrinol 31:167–186, 1983

    Google Scholar 

  3. Heldin CH, Westermark B: Growth factors: Mechanisms of action and relation to oncogenes. Cell 37:9–20, 1984

    Google Scholar 

  4. Sporn MB, Roberts AB: Autocrine growth factors and cancer. Nature 31:745–747, 1985

    Google Scholar 

  5. Heldin CH, Westermark B, Wasteson A: Specific receptors for PDGF on cells derived from connective tissue and glia. Proc Natl Acad Sci USA 78:3664–3668, 1981

    Google Scholar 

  6. Yarden Y, Escobedo JA, Kuang W-J, Yang-Feng TL, Daniel TO, Tremble PT, Chen EY, Ando ME, Harkins RN, Francke U, Fried VA, Ullrich A, Williams LT: Structure of the receptor for platelet-derived growth factor helps define a family of closely related growth factor receptors. Nature 323:226–232, 1986

    Google Scholar 

  7. Westermark B: Density dependent proliferation of human glia cells stimulated by EGF. Biochem Biophys Res Comm 69:304–310, 1976

    Google Scholar 

  8. Doolittle RF, Hunkapiller MW, Hood LE: Simian sarcoma virus one gene v-sis is derived from the gene (or genes) encoding a PDGF. Science 221:275–277, 1983

    Google Scholar 

  9. Leal F, Williams LT, Robbins KC, Aaronson SA: Evidence that the v-sis gene product transforms by interaction with the receptor for platelet-derived growth factor. Science 230:327–330, 1985

    Google Scholar 

  10. Downward J, Yarden Y, Mayes E: Close similarity of EGF receptors and v-erb B protein sequences. Nature 307:521–527, 1984

    Google Scholar 

  11. Dalla-Favera RC, Gallo RC, Giallorgo A: Chromosomal localization of the human homologue (c-sis) of the SSV one gene. Science 218:686–688, 1982

    Google Scholar 

  12. Davies RL, Gross VA, Kucherlapati R: Genetic analysis of EGF action: Assignment of human EGF receptor gene to chromosome 7. Proc Natl Acad Sci USA 77:4188–4192, 1980

    Google Scholar 

  13. Kondo I, Shimizu N: Mapping of the human gene for EGFR on the P13-q22 region of Ch 7. Cytogenet Cell Genet 35:9–14, 1983

    Google Scholar 

  14. Al Saadi A, Latimer F: Cytogenic and clinical correlations in neolasms of the human nervous system. Proc Am Assoc Cancer Res 24:10, 1983

    Google Scholar 

  15. Bigner SH, Mark J, Mahaley S, Bigner DD: Patterns of the early, gross chromosomal changes in human gliomas. Hereditas 101:103–113, 1984

    Google Scholar 

  16. Rosenblum ML, Gerosa MA, Wilson CB, Barger GR, Pertuiset BF, deTribolet N, Dougherty DV: Stem cell studies of human malignant brain tumors. J Neurosurg 58:170–176, 1983

    Google Scholar 

  17. Huang JS, Huang SS, Deuel TF: Transforming protein of simian sarcoma virus stimulates autocrine growth of SSV-transformed cells through PDGF cell-surface receptors. Cell 39:79–87, 1984

    Google Scholar 

  18. Williams LT, Tremble PM, Lavin MF, Sunday ME: Platelet-derived growth factor receptors form a high affinity state in membrane preparations. J Biol Chem 259:5287–5292, 1984

    Google Scholar 

  19. Frackelton AR, Tremble PM, Williams LT Evidence for the platelet-derived growth factor stimulated tyrosine phosphorylation of the PDGF receptor in vivo: Immunopurification using a monoclonal antibody to phosphotyrosine. J Biol Chem 259:7909–7915, 1984

    Google Scholar 

  20. Chirgwin IM, Przybyla AE, MacDonald RJ, Butler WJ: Isolation of biologically active RNA from sources enriched in ribonuclease. Biochemistry 18:5294–5299, 1979

    Google Scholar 

  21. Daniel TO, Gibbs VC, Milfay DF, Williams LT. Thrombin stimulates c-sis gene expression in microvascular endothelial cells. J Biol Chem 261:9579–9581, 1986

    Google Scholar 

  22. Haigler H, Ash JF, Singer SJ, Cohen S: Visualization by fluorescence of the binding and internalization of EGF in human carcinoma cells A431. Proc Natl Acad Sci USA 75:3317–3321, 1978

    Google Scholar 

  23. Filmus J, Pollak MN, Cairnecross JG, Buick RN: Amplified, overexpressed and rearranged EGF receptor gene in a human astrocytoma cell line. Biochem Biophys Res Comm 131:207–215, 1986

    Google Scholar 

  24. Owen AJ, Pantazis P, Antoniades HN: Simian sarcoma virus-transformed cells secrete a mitogen identical to PDGF. Science 225:54–56, 1984

    Google Scholar 

  25. Bishop JM: Cellular oncogenes and retroviruses. Ann Rev Biochem 52:301–354, 1983

    Google Scholar 

  26. Gordon H: Oncogones. Mayo Clin Proc 60:697–713, 1985

    Google Scholar 

  27. Land H, Parada LF, Weinberg RA: Cellular oncogenes and multistep carcinogenesis. Science 222:771–778, 1983

    Google Scholar 

  28. Liberman TA, Razon N, Bartal AD: Expression of EGF receptors in human brain tumors. Cancer Res 44:753–760, 1984

    Google Scholar 

  29. Bell CW, Harsh GR, Rosenblum ML, Meltzer P, Trent J: Numeric and structural alterations of chromosome 7 in human brain tumors: Correlation with expression of epidermal growth factor receptors. Proc AACR 27:37, 1986

    Google Scholar 

  30. Liberman TA, Nusbaum HR, Rason N: Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumors of glial origin. Nature 313:144–147, 1985

    Google Scholar 

  31. Westphal M, Harsh GR, Rosenblum ML, Hammonds RG: Epidermal growth factor receptors in the human glioblastoma cell line SF 268 differ from those in epidermoid carcinoma cell line A 431. Biochem Biophys Res Comm 132:284–289, 1985

    Google Scholar 

  32. Helmeste DM, Wells A, Harsh GR: Characterization of an aberrant epidermal growth factor receptor in human glioblastoma cell line SF 268. J Endocrinol (in press)

  33. Bowen-Pope DF, Vogel A, Ross R: Production of PDGF-like molecules and reduced expression of PDGF receptors accompany transformation by a wide spectrum of agents. Proc Natl Acad Sci USA:2396–2400, 1984

    Google Scholar 

  34. Nister M, Heldin CH, Wasteson A: A glioma-derived analog to PDGF: Demonstration of receptor competing activity and immunological cross reactivity. Proc Natl Acad Sci USA 81:926–930, 1984

    Google Scholar 

  35. Eva A, Robbins KC, Andersen PR: Cellular genes analogous to retroviral one genes are transcribed in human tumor cells. Nature 295:116–119, 1982

    Google Scholar 

  36. Betsholtz C, Heldin CH, Nister M: Synthesis of a PDGF-like growth factor in human glioma and sarcoma cells suggests the expression of the cellular homologue to the transforming protein of SSV. Biochem Biophys Res Commun 117:176–182, 1983

    Google Scholar 

  37. Graves DT, Owen AJ, Barth RK, Tempst P, Winoto A, Fors L, Hood LE, Antonaide HN: Detection of c-sis transcripts and synthesis of PDGF like proteins by human osteosarcoma cells. Science 226:972–974, 1984

    Google Scholar 

  38. Pantazis P, Pelicci PG, Dalla-Favera R, Antoniades HN: Synthesis and secretion of proteins resembling platelet-derived growth factor by human glioblastoma and fibrosarcoma cells in culture. Proc Natl Acad Sci USA 82:2404–2408, 1985

    Google Scholar 

  39. Epenetos AA, Courtnay-Luck N, Pickering D, Hooker G, Durbin H, Lavender JP, McGenzie CG: Antibody guided irradiation of brain glioma by arterial infusion of radioactive monoclonal antibody against epidermal growth factor receptor and blood group antigen A. Br Med J 290:1463–1466, 1985

    Google Scholar 

  40. Johnsson A, Betsholtz C, Heldin CH, Westermark B: Antibodies against PDGF inhibit acute transformation by simian sarcoma virus. Nature 317:438–442, 1985

    Google Scholar 

  41. Norris JS, Cornell LE, Hardin JW, Kohler PO, MacLeod SL, Srivatava A, Syms AJ, Smith RG: Autocrine regulation of growth II: Glucocorticoids inhibit transcription of c-sis oncogene-specific RNA transcripts. Biochem Biophys Res Comm 122:124–128, 1984

    Google Scholar 

  42. Lin SL, Kikuchi T, Pledger WJ, Tamm I: Interferon inhibits the establishement of competence in G0/S transition. Science 233:356–359, 1986

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Harsh, G.R., Rosenblum, M.L. & Williams, L.T. Oncogene-related growth factors and growth factor receptors in human malignant glioma-derived cell lines. J Neuro-Oncol 7, 47–56 (1989). https://doi.org/10.1007/BF00149378

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00149378

Key words

Navigation