Skip to main content
SpringerLink
Log in

An antisense EGFR oligodeoxynucleotide enveloped in lipofectinR induces growth inhibition in human malignant gliomas in vitro

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

Abstract

Epidermal growth factor receptor (EGFR) plays an important role in the progression of malignancy in gliomas. We studied the growth inhibition of the malignant glioma cell lines using an antisense EGFR oligodeoxynucleotide enveloped with LipofectinR. At a concentration of 5 μM of the antisense EGFR oligodeoxynucleotide enveloped with LipofectinR, the proliferation of three malignant glioma cell lines was significantly inhibited (p < 0.05) compared with that of the cells exposed to 5 μM sense EGFR oligodeoxynucleotide. The activity of the tyrosine kinase and the DNA synthesis was also significantly suppressed (p < 0.05). These findings show that the antisense EGFR oligodeoxynucleotide enveloped with LipofectinR has a possibility to become a useful gene therapy against malignant gliomas.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Libermann TA, Nusbaum HR, Razon N, Kris R, Lax I, Soreq H, Whittle N, Waterfield MD, Ullrich A, Schlessinger J: 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 

  2. Ullrich A, Coussens L, Hayflick JS, Dull TJ, Gray A, Tam AW, Lee J, Yarden Y, Libermann TA, Schlessinger J, Downward J, Mayes ELV, Whittle N, Waterfield MD, Seeburg PH: Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. Nature 309: 418–425, 1984

    Google Scholar 

  3. Greenfield C, Hiles I, Waterfield MD, Federwisch W, Wollmer A, Blundell T, McDonald N: Epidermal growth factor binding induces a conformational change in the external domain of its receptor. EMBO J 8: 4115–4123, 1989

    Google Scholar 

  4. Lin CR, Chen WS, Kruiger W, Stolarsky WS, Weber W, Evens EM, Verma IM, Gill GN, Rosenfeld MG: Expression cloning of human EGF receptor complementary DNA; gene amplification and three related messenger RNA products in A431 cells. Science 224: 843–848, 1984

    Google Scholar 

  5. Carpenter G, Zendegui J: Epidermal growth factor its receptor and related proteins. Exp Cell Res 164: 1–10, 1986

    Google Scholar 

  6. Inman WH, Carpenter G: In development and recognition of the transformed cell. In: Green MI, Hamaoka T (eds) Plenum, New York, 111–121, 1987

    Google Scholar 

  7. Hendler FJ, Ozanne BW: Human squamous cell lung cancers express increased epidermal growth factor receptors. J Clin Invest 74: 647–651, 1984

    Google Scholar 

  8. Neal DE, Marsh C, Bennett MK, Abel PD, Hall RR, Sainsbury JRC, Harris AL: Epidermal-growth-factor receptors in human bladder cancer: comparison of invasive and superficial tumors. Lancet i: 366–368, 1985

    Google Scholar 

  9. Gullick WJ, Marden JJ, Whittle N, Ward B, Bobrow L, Waterfield MD: Expression of epidermal growth factor receptors on human cervical, ovarian, and vulval carcinomas. Cancer Res 46: 285–292, 1986

    Google Scholar 

  10. Xu YH, Richert N, Ito S, Merlino GT, Pastan I: Characterization of epidermal growth factor receptor gene expression in malignant and normal human cell lines. Proc Natl Acad Sci USA 81: 7308–7312, 1984

    Google Scholar 

  11. Ekstrand AJ, James CD, Cavenee WK, Selinger B, Pettersson RF, Collins VP: The genes for epidermal growth factor receptor, transforming growth factor — alpha and epidermal growth factor and their expression in human glioblastomas in vivo. Cancer Res 51: 2164–2172, 1991

    Google Scholar 

  12. Sugawa N, Ekstrand AJ, James CD, Collins VP: Identical splicing of aberrant epidermal growth factor receptor transcript from amplified rearranged genes in human glioblastomas. Proc Natl Acad Sci USA 87: 8602–8606, 1990

    Google Scholar 

  13. Yamazaki H, Fukui Y, Ueyama Y, Tamaoki N, Kawamoto T, Taniguchi S, Masabumi S: Amplification of the structurally and functionally altered epidermal growth factor receptor gene (c-erbB) in human brain tumors. Mol Cell Biol 8: 1816–1820, 1988

    Google Scholar 

  14. Humphrey PA, Wang AJ, Vogelstein B, Zalutsky MR, Fuller GN, Archer GE, Friedman HS, Kwatra MM, Bigner SH, Bigner DD: Antisynthetic peptide antibody reacting at the fusion junction of delesion-mutant epidermal growth factor receptors in human glioblastoma. Proc Natl Acad Sci USA 87: 4207–4211, 1990

    Google Scholar 

  15. Ekstrand AJ, Sugawa N, James CD, Collins VP: Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N-and/or C-terminal trials. Proc Natl Acad Sci USA 89: 4309–4313, 1992

    Google Scholar 

  16. Arai K, Horie Y, Kurimoto M, Endo S, Hiraga K, Takaku A: A cell line of human malignant astrocytoma producing autocrine growth factor. In vitro cell. Dev Biol 27A: 606–614, 1991

    Google Scholar 

  17. Noonan KE, Roninson IB: mRNA phenotyping by enzy matic amplification of randomly primed cDNA. Nucleic Acids Res 16: 10366, 1988

    Google Scholar 

  18. Packer RJ, Sutton LN, Goldwein JW, Perilongo C, Bunin G, Ryan J, Cohen BH, D'Angio G, Kramer ED, Zimmerman RA: Improved survival with the use of adjuvant chemotherapy in the treatment of medulloblastoma. J Neurosurg 74(3): 433–440, 1991

    Google Scholar 

  19. Walker MD: Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas, a cooperative clinical trial. J Neurosurgery 49: 333–343, 1978

    Google Scholar 

  20. Ekstrand AJ, Longo N, Collins VP, James CD: Functional analysis of an epidermal growth factor receptor with a truncation in the extracellular domain that is frequently produced in glioblastoma with EGFR amplification. J Neuro-Oncol 15(Suppl): S8, 1993

    Google Scholar 

  21. Colomer G, Lupu R, Bacus SS, Gelmann EP: erbB-2 antisense oligonucleotides inhibit the proliferation of breast carcinoma cells with erbB-2 oncogene amplification. Br J Cancer 70: 819–825, 1994

    Google Scholar 

  22. Yagi K, Noda H, Kurono M, Ohishi N: Efficient gene transfer with less cytotoxicity by means of cationic multilamellar liposomes. Biochem Biophys Res Commun 196: 1042–1048, 1993

    Google Scholar 

  23. Yagi K, Nishikimi M, Hayashi Y: Incorpolation of histone into liposomes increases the efficiency of liposome-mediated gene transfer. J Clin Biochem Nutr 10: 21–25, 1991

    Google Scholar 

  24. Nishikawa R, Ji XD, Harmon RC, Lazar CS, Gill GN, Cavenee WK, Huang HJ: A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity. Proc Natl Acad Sci USA 91: 7727–7731, 1994

    Google Scholar 

  25. Nister M, Libermann T, Betsholtz C, Pettersson M, Claesson-Welsh L, Heldin C-H, Schlessinger J, Westermark B: Expression of messenger RNAs for platelet-derived growth factor and transforming growth factor-a and their receptors in human malignant glioma cell lines. Cancer Res 48: 3910–3918, 1988

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Kyoto Prefectural University of Medicine, Japan

    Noriaki Sugawa, Satoshi Ueda & Yoshio Nakagawa

  2. Department of Biochemistry, Kyoto Prefectural University of Medicine, Japan

    Hoyoku Nishino, Kazuto Nosaka & Akio Iwashima

  3. Department of Neurosurgery, Toyama Medical and Pharmacology, Japan

    Masanori Kurimoto

Authors
  1. Noriaki Sugawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Satoshi Ueda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoshio Nakagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hoyoku Nishino
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kazuto Nosaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Akio Iwashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Masanori Kurimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sugawa, N., Ueda, S., Nakagawa, Y. et al. An antisense EGFR oligodeoxynucleotide enveloped in lipofectinR induces growth inhibition in human malignant gliomas in vitro. J Neurooncol 39, 237–244 (1998). https://doi.org/10.1023/A:1005903002865

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1005903002865

Search

Navigation