Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Fundamental study of small interfering RNAs for ganglioside GD3 synthase gene as a therapeutic target of lung cancers

Oncogene volume 25, pages 6924–6935 (2006)Cite this article

Abstract

Gangliosides GD3 and GD2 are specifically expressed in neuro-ectoderm-derived tumors, and are considered to play roles in the malignant properties of those cells. We analysed effects of small interfering (si) RNAs against GD3 synthase gene on the expression of ganglioside GD2 and biological phenotypes of human lung cancer cells expressing GD2. An siRNA could suppress the mRNA level of GD3 synthase gene even by single transfection, whereas repeated transfection was required to suppress GD2 expression on the cell surface. Significant reduction in the cell growth and invasion activity was observed in both lung cancer cell lines examined, when repeatedly transfected with the siRNA twice a week. DNA ladder formation was observed after third transfection, indicating the potent induction of apoptosis. Stable transfection of an RNAi expression vector with H1 RNA promoter was also examined. Transfectant cells with the RNAi expression vector showed almost equivalent suppression of GD2 expression and tumor properties in vitro. Furthermore, the stable transfectant cells showed slower cell growth than the control cells in severe combined immunodeficiency mice. These results suggested that siRNAs and/or RNAi expression vectors to generate siRNAs are promising approach to overcome human lung cancers.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10
Figure 11
Figure 12

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  • Aixinjueluo W, Furukawa K, Zhang Q, Hamamura K, Tokuda N, Yoshida S et al. (2005). J Biol Chem 80: 29828–29836.

  • Aoki H, Satoh M, Mitsuzuka K, Ito A, Saito S, Funato T et al. (2004). FEBS Lett 567: 203–208.

  • Bai X, Zhou D, Brown JR, Crawford BE, Hennet T, Esko JD . (2001). J Biol Chem 276: 48189–48195.

  • Barik S . (2004). Ann Med 36: 540–551.

  • Brummelkamp TR, Bernards R, Agami R . (2002). Science 296: 550–553.

  • Carubia JM, Yu RK, Macala LJ, Kirkwood JM, Varga JM . (1984). Biochem Biophys Res Commun 120: 500–504.

  • Damstrup L, Voldborg BR, Span-Thomser M, Brünner N, Poulsen HS . (1998). Br J Cancer 78: 631–640.

  • Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T . (2001). Nature 411: 494–498.

  • Fenderson BA, Eddy EM, Hakomori S . (1990). Bioessays 12: 173–179.

  • Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC . (1998). Nature 391: 806–811.

  • Fukumoto S, Mutoh T, Hasegawa T, Miyazaki H, Okada M, Goto G et al. (2000). J Biol Chem 275: 5832–5838.

  • Furukawa K, Arita Y, Satomi N, Eisinger M, Lloyd KO . (1990). Arch Biochem Biophys 281: 70–75.

  • Hakomori S . (1990). J Biol Chem 265: 18713–18716.

  • Hakomori S . (2002). Proc Natl Acad Sci USA 99: 10231–10233.

  • Hamamura K, Furukawa K, Hayashi T, Hattori T, Nakano J, Nakashima H et al. (2005). Proc Natl Acad Sci USA 102: 11041–11046.

  • Haraguchi M, Yamashiro S, Yamamoto A, Furukawa K, Takamiya K, Lloyd KO et al. (1994). Proc Natl Acad Sci USA 91: 10455–10459.

  • Hauck CR, Hsia DA, Puente XS, Cheresh DA, Schlaepfer DD . (2002). EMBO J 21: 6289–6302.

  • Houghton AN, Mintzer D, Cordon-Cardo C, Welt S, Fliegel B, Vadhan S et al. (1985). Proc Natl Acad Sci USA 82: 1242–1246.

  • Izquierdo M . (2005). Cancer Gene Ther 12: 217–227.

  • Kojima Y, Fukumoto S, Furukawa K, Okajima T, Wiels J, Yokoyama K et al. (2000). J Biol Chem 275: 15152–15156.

  • Okada M, Furukawa K, Yamashiro S, Yamada Y, Haraguchi M, Horibe K et al. (1996). Cancer Res 56: 2844–2848.

  • Portoukalian J, Zwingelstein G, Dore JF . (1979). Eur J Biochem 94: 19–23.

  • Pukel CS, Lloyd KO, Travassos LR, Dippold WG, Oettgen HF, Old LJ . (1982). J Exp Med 155: 1133–1147.

  • Schengrund CL . (1990). Brain Res Bull 24: 131–141.

  • Scherer L, Rossi JJ . (2004). Curr Pharm Biotechnol 5: 355–360.

  • Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada T, Harano T et al. (2004). Cancer Res 64: 3753–3760.

  • Waterhouse PM, Wang MB, Lough T . (2001). Nature 411: 834–842.

  • Yoshida S, Fukumoto S, Kawaguchi H, Sato S, Ueda R, Furukawa K . (2001). Cancer Res 61: 4244–4252.

  • Yu RK, Macala LJ, Taki T, Weinfield HM, Yu FS . (1988). J Neurochem 50: 1825–1829.

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry II, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan

    K Ko, K Furukawa, T Urano & K Furukawa

  2. Department of Surgery, Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan

    K Ko, M Nagino & Y Nimura

  3. Department of Molecular Oncology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan

    T Takahashi

  4. Department of Biochemical Cell Research, Tokyo Metropolitan Institute of Medical Science, Honkomagome, Bunkyo-Ku, Tokyo, Japan

    Y Sanai

  5. Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai City, Aichi, Japan

    K Furukawa

Authors
  1. K Ko
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K Furukawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T Urano
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Y Sanai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M Nagino
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Y Nimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. K Furukawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K Furukawa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ko, K., Furukawa, K., Takahashi, T. et al. Fundamental study of small interfering RNAs for ganglioside GD3 synthase gene as a therapeutic target of lung cancers. Oncogene 25, 6924–6935 (2006). https://doi.org/10.1038/sj.onc.1209683

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1209683

Keywords

This article is cited by

Search

Advanced search

Quick links