ras Oncogenes pp 165-174 | Cite as

Suppression of ras Oncogene Expression Using Sequence Specific Oligodeoxynucleotides

  • P. Hawley
  • I. Gibson

Abstract

The activation of ras oncogenes has been clearly implicated in the tumorigenic process, being the oncogene most frequently identified in human cancers. (Barbacid 1985). Ras genes containing point mutations as well as amplified genes leading to over-expression of the protein product p21 have been found in human tumours (Der et al 1982, Bos et al 1986). There is, however, no reason to assume that we have yet identified all of the genetic changes involved or indeed that they are necessarily the primary events in tumorigenesis.

Keywords

Antisense Oligonucleotide Tissue Culture Medium EC816 Cell Porated Cell EC816 Cell Line 
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. Barbacid, M. (1985). In “Important Advances in Oncology 1986” ed. V de Vita, S. Hellman, S. Rosenberg, pp 3–22. Philadelphia Lippincot.Google Scholar
  2. Bos, J. L., Toksoz, D., Marshall, C., J and 6 others (1986). Amino acid substitutions at codon 13 in the N-ras oncogene in human acute mycloid leukaemia. Nature 315, 726.CrossRefGoogle Scholar
  3. Cazenave, C., Loreau, N., Thuong, N.T., Toulemé, J.J. and Hélène, C. (1987). Enzymatic amplification of translation inhibition of rabbit b-globin in RNA mediated by anti mesenger oligodeoxynucleotides covalently linked to intercalting agents. Nucleic Acids Res. 15, 4717.PubMedCrossRefGoogle Scholar
  4. Cohen, J.B. and Levinson, A.D. (1988). A point mutation in the last intron responsible for increased expression and transforming activity of the c-Ha-ras oncogenes. Nature 334 119.PubMedCrossRefGoogle Scholar
  5. 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 & Kirsten carcinoma viruses. Proc. Natl. Acad. Sci. USA 79, 3637–3640.PubMedCrossRefGoogle Scholar
  6. Heikki la, R., Schwab G., Wickstrom, E. and 4 others. (1987). Ac-myc antisense oligodeoxynucleotide inhibits entry in S phase but not progress from G0-G1. Nature 328, 445.PubMedCrossRefGoogle Scholar
  7. Holt, J.T., Redner, R.L. and Neinhuis, A.W. (1987). An oligomer complementary to c-myc inhibits proliferation of HL60 promyclocytic cells and induces differentiation. Mol. Cell Biol. 8, 963.Google Scholar
  8. Li, Y., Seyama, T., Godison, A. K., Winokun, T. S., Lebovitz, R.M. and Lieberman, M.W. (1988). MTras T24, a metallothionein-ras fusion gene, modulates expression in cultured rat liver cells of two genes associated with in vivo liver cancer. Proc. Natl. Acad. Sci. USA 85, 344–348.PubMedCrossRefGoogle Scholar
  9. Linstead, P., Jennings, B., Prescott, A., Hawley, P., Warn, R., Gibson, I. (1988). Scanning electron microscopy and the transformed phenotype. Micron and Microsc. Acta 19, 155–162.Google Scholar
  10. Maher, L.J. ad Dolnick, B.J. (1987). Specific hybridization arrest of dihydrofolate reductase in RNA in vitro using anti-sense RNA or anti-sense oligonucleotides. Arch. Biochem and Biophys. 252 (1), 214–220.CrossRefGoogle Scholar
  11. McKay, I.A., Marshall, C. J., Cales, C. and Hall, A. (1986). Transformation and stimulation of DNA synthesis in NIH 3T3 cells are a titratable function of normal p21 N-ras expression. EMBO Journal 157.Google Scholar
  12. Reynolds V. L., Lebovitz, R. M., Warren, S., Hawley, T. S., Godwin, A.K., Lieberman, M.W. (1987). Regulation of a metallothionein-ras T24 fusion gene by zinc results in graded alterations in cell morphology and growthn.Google Scholar
  13. Smith, C.C., Aurelian, L., Reddy, M.P., Miller, P.S. and Ts ’O, P.O.P. (1986). Antiviral effect of an oligo (nucleoside methylphosphonate) complementary to the splice junction of herpes simplex virus type 1 immediate early pre mRNAs 4 and 5. Proc. Natl. Acad. Sci. USA 83 2787–2791.PubMedCrossRefGoogle Scholar
  14. Stein, C.A. and Cohen, J.S. (1988). Oligodeoxynucleotides as inhibitors of gene expression: A review. Cancer Res. 48, 2659–2668.PubMedGoogle Scholar
  15. Tidd, D. M., Hawley, P., Warenius, H.M. and Gibson, I. (1988). Evaluation of N-ras oncogene anti-sense, sense and nonsense sequence methylphosphonate oligonucleotide analogues. Anti Cancer Drug Design 3, 117–127.PubMedGoogle Scholar
  16. Wickstrom, E. L., Wickstrom, E., Lyman, G.H. and Freeman, D.L. (1986). HL60 cell proliferation inhibited by an anti-c-myc pentadecadeoxynucleotide. Federation proceedings, 1708.Google Scholar
  17. Winterbourne, D.J., Thomas, S., Herman-Taylor, J., Hussain, I., Johnston, Alan P. (1988). Electric shock mediated transfection of cells. Biochem. J. 251, 427–434.PubMedGoogle Scholar
  18. Zamecnik, P.C., Goodchild, J., Taguchi, Y. and Sarin, P.S. (1986). Inhibition of replication and expression of human T-cell lymphotropic virus type III in cultured cells by exogenous synthetic oligonucleotides complementary to viral RNA. Proc. Natl. Acad. Sci. USA, 83, 4143.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • P. Hawley
    • 1
  • I. Gibson
    • 1
  1. 1.School of Biological SciencesUniversity of East AngliaNorwichUK

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