Skip to main content
Log in

Major structural alterations of the c-sis gene are not observed in a series of tumors of the human central nervous system

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

Abstract

Expression of the c-sis oncogene, the gene encoding the B chain of platelet-derived growth factor (PDGF), may be related to initiation and/or progression of glial cell tumorigenesis by PDGF-mediated autocrine growth stimulation. As the mechanism for activation of expression of the c-sis gene in gliomas is not known, we searched for possible structural alterations of c-sis DNA in these tumors. Genomic Southern blots of DNA from 7 different cultured human glioblastoma cell lines and 15 different solid human brain tumors revealed no significant change in either the gross structure or the copy number of the c-sis gene in tumor cells vs. control cells. Activation of glioma c-sis gene expression is therefore not the result of a gross rearrangement or amplification of the c-sis gene. Expression of c-sis mRNA was detected in all of 12 different solid human brain tumors, 11 of which were of glial cell origin. However, in tissue adjacent to 5 different tumors, approximately the same level of c-sis mRNA was seen.

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. Nishimura S, Sekiya T: Human cancer and cellular oncogenes. Biochem J 243:313–327, 1987

    PubMed  Google Scholar 

  2. Chiu IM, Reddy EP, Givol D, Robbins KC, Tronick SR, Aaronson SA: Nucleotide sequence analysis identifies the human c-sis proto-oncogene as a structural gene for platelet-derived growth factor. Cell 37:123–129, 1984

    Article  PubMed  Google Scholar 

  3. Johnsson A, Heldin C-H, Wasteson A, Westermark B, Deuel T, Huang JS, Seeburg PH, Gray A, Ullrich A, Scrace G, Stroobant P, Waterfield MD: The c-sis gene encodes a precursor of the B chain of platelet-derived growth factor. EMBO J 3:921–928, 1984

    PubMed  Google Scholar 

  4. Heldin C-H, Westermark B, Wasteson A: Specific receptors for platelet derived growth factor in cells derived from connective tissue and glia. Proc Natl Acad Sci USA 78:3664–3668, 1981

    PubMed  Google Scholar 

  5. Eva A, Robbins KC, Andersen PR, Srinivasan A, Tronick SR, Reddy EP, Ellmore NW, Galen AT, Lautenberger TJ, Papas TS, Westin EH, Wong-Staal F, Gallo RE, Aaronson SA: Cellular genes analogous to retroviral oncogenes are transcribed in human tumor cells. Nature 295:116–119, 1982

    Article  PubMed  Google Scholar 

  6. 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 82:2404–22408, 1985

    PubMed  Google Scholar 

  7. Betsholtz C, Johnsson A, Heldin C-H, Westermark B, Lind P, Urdea MS, Eddy R, Shows TB, Philpott K, Mellor AL, Knott TJ, Scott J: cDNA sequence and chromosomal localization of human platelet derived growth factor A-chain and its expression in tumor cell lines. Nature 320:695–699, 1986

    Article  PubMed  Google Scholar 

  8. Press RD, Samols D, Goldthwait DA: The expression and stability of c-sis mRNA in human glioblastoma cells. Biochemistry 27:5736–5741, 1988

    Article  PubMed  Google Scholar 

  9. Betsholtz C, Heldin C-H, Nister M, Ek B, Wasteson A, Westermark B: 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 simian sarcoma virus. Biochem Biophys Res Commun 117:176–182, 1983

    Article  PubMed  Google Scholar 

  10. Nister M, Heldin C-H, Wasteson A, Westermark B: A glioma-derived analog to platelet-derived growth factor: demonstration of receptor competing activity and immunological crossreactivity. Proc Natl Acad Sci USA 81:926–930, 1984

    PubMed  Google Scholar 

  11. Nister M, Heldin C-H, Westermark B: Clonal variation in the production of platelet-derived growth factor-like protein and expression of corresponding receptors in a human malignant glioma. Cancer Res 46:332–340, 1986

    PubMed  Google Scholar 

  12. Southern EM: Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98: 503–517, 1975

    PubMed  Google Scholar 

  13. Devare SG, Reddy EP, Law JD, Robbins KC, Aaronson SA: Nucleotide sequence of the simian sarcoma virus genome: demonstration that its acquired cellular sequences encode the transforming gene product p28sis Proc Natl Acad Sci USA 80:731–735, 1983

    PubMed  Google Scholar 

  14. Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ: Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18:5294–5299, 1979

    Article  PubMed  Google Scholar 

  15. Dalla-Favera R, Gallo RC, Giallongo A, Croce CM: Chromosomal localization of the human homolog (c-sis) of the simian sarcoma virus oncogene. Science 218:686–688, 1982

    PubMed  Google Scholar 

  16. Rao CD, Igarashi H, Chiu IM, Robbins KC, Aaronson SA: Structure and sequences of the human c-sis/platelet-derived growth factor 2 (sis/PDGF2) transcriptional unit. Proc Natl Acad Sci USA 83:2392–2396, 1986

    PubMed  Google Scholar 

  17. Dalla-Favera R, Gelmann EP, Gallo RC, Wong-Staal F: A human oncogene homologous to the transforming gene (v-sis) of simian sarcoma virus. Nature 292:31–35, 1981

    Article  PubMed  Google Scholar 

  18. Van den Ouweland AMW, Breuer ML, Steenbergh PH, Schalken JA, Bloemers HPJ, Van den Ven WJM: Comparative analysis of the human and feline c-sis proto-oncogenes. Identification of 5′ human c-sis coding sequences that are not homologous to the transforming gene of simian sarcoma virus. Biochim Biophys Acta 825:140–147, 1985

    PubMed  Google Scholar 

  19. Barrett TB, Gajdusek CM, Schwartz SM, McDougall JK, Benditt EP: Expression of the sis gene by endothelial cells in culture andin vivo. Proc Natl Acad Sci 81:6772–6774, 1984

    PubMed  Google Scholar 

  20. Jaye M, McConthy E, Drohan W, Tong B, Deuel T, Maciag T: Modulation of the sis gene transcript during endothelial cell differentiationin vitro. Science 228:882–885, 1985

    PubMed  Google Scholar 

  21. Nister M, Wedell B, Betsholtz C, Bywater M, Pettersson M, Westermark B, Mark J: Evidence for progressional changes in the human malignant glioma line U343-MGa: Analysis of karyotype and expression of genes encoding the subunit chains of platelet-derived growth factor. Cancer Res 47:4953–4960, 1987

    PubMed  Google Scholar 

  22. Clarke MF, Westin E, Schmidt D, Josephs SF, Ratner L, Wong-Staal F, Gallo RC, Reitz MS: Transformation of NIH 3T3 cells by a human c-sis cDNA clone. Nature 308: 464–467, 1984

    Article  PubMed  Google Scholar 

  23. Gazit A, Igarashi H, Chiu IM, Srinivasan A, Yaniv A, Tronick S, Robbins KC, Aaronson SA: Expression of the normal human sis/PDGF-2 coding sequence induces cellular transformation. Cell 39:89–97, 1984

    Article  PubMed  Google Scholar 

  24. Daniel TO, Gibbs VC, Milfay DF, Garovoy MR, Williams LT: Thrombin stimulates c-sis gene expression in microvascular endothelial cells. J Biol Chem 261:9579–9582, 1986

    PubMed  Google Scholar 

  25. Alitalo R, Andersson LC, Betsholtz C, Nilsson K, Westermark B, Heldin C-H, Alitalo K: Induction of plateletderived growth factor gene expression during megakaryoblastic and monocytic differentiation of human leukemia cell lines. EMBO J 6:1213–1218, 1987

    PubMed  Google Scholar 

  26. Colamonici OR, Trepel JB, Vidal CA, Neckers LM: Phorbol ester induces c-sis gene transcription in stem cell line K-562. Mol Cell Biol 6:1847–1850, 1986

    PubMed  Google Scholar 

  27. Makela TP, Alitalo R, Paulson Y, Westermark B, Heldin C-H, Alitalo K: Regulation of platelet-derived growth factor gene expression by transforming growth factor B and phorbol ester in human leukemia cell lines. Mol Cell Biol 7: 3656–3662, 1987

    PubMed  Google Scholar 

  28. Pantazis P, Sariban E, Kufe D, Antoniades HN: Induction of c-sis gene expression and synthesis of platelet derived growth factor in human myeloid leukemia cells during monocytic differentiation. Proc Natl Acad Sci 83:6455–6459, 1986

    PubMed  Google Scholar 

  29. Daniel TO, Gibbs VC, Milfay DF, Williams LT: Agents that increase cAMP accumulation block endothelial c-sis induction by thrombin and transforming growth factor-β. J Biol Chem 262:11893–11896, 1987

    PubMed  Google Scholar 

  30. Leof EB, Proper TA, Goustin AS, Shipley GD, Dicorleto PE, Moses HL: Induction of c-sis mRNA and activity similar to platelet derived growth factor by transforming growth factor β: A proposed model for indirect mitogenesis involving autocrine activity. Proc Natl Acad Sci 83:2453–2457, 1986

    PubMed  Google Scholar 

  31. Derynck R, Jarrett JA, Chen EY, Eaton DH, Bell JR, Assoian RK, Roberts AB, Sporn MB, Gouddel DV: Human transforming growth factor β complementary DNA sequence and expression in normal and transformed cells. Nature 316:701–705, 1985

    PubMed  Google Scholar 

  32. Derynck R, Goeddel R, Ullrich A, Gutterman JU, Williams RD, Bringman TS, Berger WH: Synthesis of messenger RNA's for transforming growth factors α and β and the epidermal growth factor receptor by human tumors. Ca Res 47:707–712, 1987

    Google Scholar 

  33. Wrann M, Bodmer S, deMartin R, Siepl C, Hofer-Warbinek R, Frei K, Hofer E, Fontana A: T cell suppressor factor from human glioblastoma cells is a 12.5 Kb protein closely related to transforming growth factor β. EMBO J 6:1633–1636, 1987

    PubMed  Google Scholar 

  34. Libermann TA, Nusbaum HR, Razon N, Kris R, Lax I, Soreq H, Whittle N, Waterfield MD, Ullrich A, Schlesinger J: Amplification, enhanced expression and possible rearrangment of EGF receptor gene in primary human brain tumors of glial origin. Nature 313:144–147, 1985

    Article  PubMed  Google Scholar 

  35. Wong AJ, Bigner SH, Bigner DD, Kinzler KW, Hamilton SR, Vogelstein B: Increased expression of the epidermal growth factor receptor gene in malignant gliomas is invariably associated with gene amplification. Proc Natl Acad Sci USA 84:6899–6903, 1987

    PubMed  Google Scholar 

  36. Trent J, Meltzer P, Rosenblum M, Harsh G, Kinzler K, Mashal R, Feinberg A, Vogelstein B: Evidence for rearrangement, amplification, and expression of c-myc in a human glioblastoma. Proc Natl Acad Sci USA 83:470–473, 1986

    PubMed  Google Scholar 

  37. Bargmann CI, Hung MC, Weinberg RA: Multiple independent activations of the neu oncogene by a point mutation altering the transmembrane domain of p 185. Cell 45:649–657, 1986

    Article  PubMed  Google Scholar 

  38. Kinzler KW, Bigner SH, Bigner DD, Trent JM, Law ML, O'Brien SJ, Wong AJ, Vogelstein B: Identification of an amplified, highly expressed gene in a human glioma. Science 236:70–73, 1987

    PubMed  Google Scholar 

  39. Birchmeier C, Sharma S, Wigler M: Expression and rearrangement of the ros-1 gene in human glioblastoma cells. Proc Natl Acad Sci USA 84:9270–9274, 1987

    PubMed  Google Scholar 

  40. Fukui M, Yamamoto T, Kawai S, Maruo K, Toyoshima K: Detection of a raf-related and two other transforming DNA sequences in human tumors maintained in nude mice. Proc Natl Acad Sci USA 82:5954–5958, 1985

    PubMed  Google Scholar 

  41. Bigner SH, Mark J, Bullard DE, Mahaley MS, Bigner DD: Chromosomal evolution in malignant human gliomas starts with specific and usually numerical deviations. Cancer Genet Cytogenet 22:121–135, 1986

    Article  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  43. Schimke RT: Gene amplification in cultured animal cells. Cell 37:705–713, 1984

    Article  PubMed  Google Scholar 

  44. Zang KD: Cytological and cytogenetical studies on human meningioma. Cancer Genet Cytogenet 6:249–274, 1982

    Article  PubMed  Google Scholar 

  45. Mark J: Chromosomal abnormalities and their specificity in human neoplasm. An assessment of recent observations by banding techniques. Adv Cancer Res 24:165–222, 1977

    PubMed  Google Scholar 

  46. Zankl H, Zang KD: Correlations between clinical and cytogenetic data in 180 meningiomas. Cancer Genet Cytogenet 1:351–356, 1980

    Article  Google Scholar 

  47. Seizinger BR, de la Monte S, Atkins L, Gusella JF, Martuza RL: Molecular genetic approach to human meningioma: Loss of genes on chromosome 22. Proc Natl Acad Sci USA 84:5419–5423, 1987

    PubMed  Google Scholar 

  48. Friend SH, Dryja TP, Weinberg RA: Oncogenes and tumor-suppressing genes. New Engl J Med 318:618–622, 1988

    PubMed  Google Scholar 

  49. Bigner SH, Bjerkvig R, Didrik-Laerum O: DNA content and chromosomal composition of malignant human gliomas. Neurological Clinics 3:769–784, 1985

    Google Scholar 

  50. Bigner SH, Mark J, Burger PC, Mahaley S, Bullard DE, Muhlbaier LH, Bigner DD: Specific chromosomal abnormalities in malignant human gliomas. Cancer Res 88:405–411, 1988

    Google Scholar 

  51. Josephs SF, Guo C, Ratner L, Wong-Staal F: Human proto-oncogene nucleotide sequence corresponding to the transforming region of simian sarcoma virus. Science 233: 487–491, 1984

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Press, R.D., Misra, A., Samols, D. et al. Major structural alterations of the c-sis gene are not observed in a series of tumors of the human central nervous system. J Neuro-Oncol 7, 345–356 (1989). https://doi.org/10.1007/BF02147092

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02147092

Key words

Navigation