You have full text access to this OnlineOpen article

Adenovirus-mediated Gene Transduction of IkB or IkB Plus Bax Gene Drastically Enhances Tumor Necrosis Factor (TNF)-induced Apoptosis in Human Gliomas

  1. Nobusada Shinoura1,2,
  2. Naoki Yamamoto1,
  3. Yoko Yoshida1,
  4. Takashi Fujita3,
  5. Nobuto Saito2,
  6. Akio Asai2,
  7. Takaaki Kirino2,4,
  8. Hirofumi Hamada1,5,*

Article first published online: 22 AUG 2005

DOI: 10.1111/j.1349-7006.2000.tb00858.x

Issue

Cancer Science

Cancer Science

Volume 91, Issue 1, pages 41–51, January 2000

Additional Information

How to Cite

Shinoura, N., Yamamoto, N., Yoshida, Y., Fujita, T., Saito, N., Asai, A., Kirino, T. and Hamada, H. (2000), Adenovirus-mediated Gene Transduction of IkB or IkB Plus Bax Gene Drastically Enhances Tumor Necrosis Factor (TNF)-induced Apoptosis in Human Gliomas. Cancer Science, 91: 41–51. doi: 10.1111/j.1349-7006.2000.tb00858.x

Author Information

  1. 1

    1Department of Molecular Biotherapy Research, Cancer Chemotherapy Center, Cancer Institute, 1–37–1 Kami-Ikebukuro, Toshima-ku, Tokyo 170–8455

  2. 2

    1Department of Neurosurgery, Tokyo University, 7–3–1 Hongo, Bunkyo-ku, Tokyo 113–8655

  3. 3

    1Department of Tumor Cell Biology, The Tokyo Metropolitan Institute of Medical Science, 3–18–22 Honkomagome, Bunkyo-ku, Tokyo 113–0021

  4. 4

    1CREST (Core Research for Evolutional Science and Technology), Tokyo

  5. 5

    1Department of Molecular Medicine, Sapporo Medical University, Sapporo, 060–8556

* To whom correspondence should be addressed at the Cancer Chemotherapy Center, Cancer Institute. E-mail: hhamada@jfcr.or.jp

Publication History

  1. Issue published online: 22 AUG 2005
  2. Article first published online: 22 AUG 2005
  3. (Received August 24, 1999/Revised October 12, 1999/Accepted October 14, 1999)

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

Get PDF (896K)

Keywords:

  • Apoptosis;
  • IkB;
  • TNF;
  • Bax;
  • Gene therapy

Tumor necrosis factor-α (TNF), which was initially supposed to be a promising cancer therapeutic reagent, does not kill most types of cancer cells partly due to the activation of an anti-apoptotic gene, NF-kB. NF-kB forms an inactive complex with the inhibitor kappa B alpha (IkBα), which is rapidly phosphorylated and degraded in response to various extracellular signals. To disrupt this protective mechanism, we introduced an inhibitor kappa B alpha (IkBdN) gene, a deletion mutant gene lacking the nucleotides for the N-terminal 36 amino acids of IkBα, into human glioma cells (U251, T-98G, and U-373MG) via an adenoviral (Adv) vector in addition to treatment of the glioma cells with recombinant TNF. Immunohistochemical analysis revealed that NF-kB was translocated to nuclei by TNF treatment in U251 and T-98G cells, but not in U-373MG cells. Neither transduction of IkBdN nor treatment with TNF protein alone induced apoptosis in U251 and T-98G cells, whereas both cell lines underwent drastic TNF-induced apoptosis after transduction of IkBdN. On the other hand, U-373MG cells were refractory to TNF-induced apoptosis even when they were transduced with the IkBdN gene. U-373MG cells underwent drastically increased apoptosis when co-transduced with the IkBdN and Bax gene in the presence of TNF. Adv-mediated transfer of IkBdN or IkBdN plus Bax may be a promising therapeutic approach to treat gliomas through TNF-mediated apoptosis.

Get PDF (896K)