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:

Tissue-specific expression of a suicide gene for selective killing of neuroblastoma cells using a promoter region of the NCX gene

Cancer Gene Therapy volume 8, pages 997–1002 (2001)Cite this article

Abstract

The human NCX gene, a homologue of the murine neural crest homeobox ( Ncx/Hox11L.1 ) gene whose expression is restricted to a subset of neural crest-derived tissues, was expressed in human neuroblastoma cells but not in other tumors or fibroblasts. A 4.5-kb genomic fragment in the 5′-flanking region of the NCX gene efficiently transcribed the fused luciferase reporter gene in human neuroblastoma cells but not in non-neuroblastoma cells. Sequential deletion of this regulatory region from the 5′ side demonstrated that a 1.7-kb fragment upstream from the start codon retained the preferential promoter activity in neuroblastoma cells. The transcriptional activation by the NCX promoter was stronger than that by the SV40 T antigen promoter in human neuroblastoma cells. Transfection of neuroblastoma cells with the NCX promoter–linked herpes simplex virus–thymidine kinase ( HSV-TK ) gene increased their sensitivity to ganciclovir. The regulatory region of the NCX gene is thus useful for neuroblastoma-specific suicide gene therapy. Cancer Gene Therapy (2001) 8, 997–1002

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

Similar content being viewed by others

References

  1. Moolten FL . Drug sensitivity (“suicide”) genes for selective cancer chemotherapy Cancer Gene Ther 1994 1: 279–287

    CAS  PubMed  Google Scholar 

  2. Roth JA, Cristiano RJ . Gene therapy for cancer: what have we done and where are we going? J Natl Cancer Inst 1997 88: 21–39

    Article  Google Scholar 

  3. Miller N, Whelan J . Progress in transcriptionally targeted and regulatable vectors for genetic therapy Hum Gene Ther 1997 8: 803–815

    Article  CAS  PubMed  Google Scholar 

  4. Wen X-Y, Tang S, Breitman ML . Genetic mapping of two mouse homeobox genes, Tlx-1 andTlx-2 to murine chromosome 19 and 6 Genomics 1994 24: 388–390

    Article  CAS  PubMed  Google Scholar 

  5. Hatano M, Iitsuka Y, Yamamoto H, et al . Ncx, a Hox11 related gene, is expressed in a variety of tissues derived from neural crest cells Anat Embryol 1997 195: 419–425

    Article  CAS  Google Scholar 

  6. Hatano M, Aoki T, Dezawa M, et al . A novel pathogenesis of megacolon in Ncx/Hox11L.1 deficient mice J Clin Invest 1997 100: 795–801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Iitsuka Y, Shimizu H, Kang MM, et al . An enhancer element for expression of the Ncx ( Enx, Hox11L1 ) gene in neural crest-derived cells J Biol Chem 1999 274: 24401–24407

    Article  CAS  PubMed  Google Scholar 

  8. Ko SC, Cheon J, Kao C, et al . Osteocalcin promoter-based toxic gene therapy for the treatment of osteosarcoma in experimental models Cancer Res 1996 56: 4614–4619

    CAS  PubMed  Google Scholar 

  9. Braiden V, Nagayama Y, Iitaka M, et al . Retrovirus-mediated suicide gene/prodrug therapy targeting thyroid carcinoma using a thyroid-specific promoter Endocrinology 1998 139: 3996–3999

    Article  CAS  PubMed  Google Scholar 

  10. Arbuthnot PB, Bralet MP, Le Jossic C, et al . In vitro and in vivo hepatoma cell-specific expression of a gene transferred with an adenoviral vector Hum Gene Ther 1996 7: 1503–1514

    Article  CAS  PubMed  Google Scholar 

  11. Su H, Chang JC, Xu SM, Kan YW . Selective killing of AFP-positive hepatocellular carcinoma cells by adeno-associated virus transfer of the herpes simplex virus thymidine kinase gene Hum Gene Ther 1996 7: 463–470

    Article  CAS  PubMed  Google Scholar 

  12. Richards CA, Austin EA, Huber BE . Transcriptional regulatory sequences of carcinoembryonic antigen: identification and use with cytosine deaminase for tumor-specific gene therapy Hum Gene Ther 1995 6: 881–893

    Article  CAS  PubMed  Google Scholar 

  13. Lan KH, Kanai F, Shiratori Y, et al . In vivo selective gene expression and therapy mediated by adenoviral vectors for human carcinoembryonic antigen-producing gastric carcinoma Cancer Res 1997 57: 4279–4284

    CAS  PubMed  Google Scholar 

  14. Blackwell TK, Kretzner L, Blackwood EM, et al . Sequence-specific DNA binding by the c-Myc protein Science 1990 250: 1149–1151

    Article  CAS  PubMed  Google Scholar 

  15. Whyatt DJ, deBoer E, Grosvelt F . The two zinc finger-like domains of GATA-1 have different DNA binding specificities EMBO J 1993 12: 4993–5005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Meck MM, Wierdl M, Wagner LM, et al . A virus-directed enzyme prodrug therapy approach to purging neuroblastoma cells from hematopoietic cells using adenovirus encoding rabbit carboxylesterase and CPT-11 Cancer Res 2001 61: 5083–5089

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant-in-aid for scientific research from the Japan Society for the Promotion of Science, a grant-in-aid for scientific research on priority areas from the Minister of Education, Culture, Sports, Science and Technology of Japan, and the Hamaguchi foundation for the advancement of biochemistry. R. Bahar is supported by the STA fellowship from the Science and Technology Agency of Japan. We thank F. Hoffman-La Roche (Basel, Switzerland) for their generous gift of GCV.

Author information

Authors and Affiliations

  1. Division of Pathology, Chiba Cancer Center Research Institute, Chiba, Japan

    Mitsuro Narita, Rumana Bahar & Masatoshi Tagawa

  2. Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan

    Mitsuro Narita, Shigemasa Goto & Hiromitsu Saisho

  3. Department of Developmental Genetics, Graduate School of Medicine, Chiba University, Chiba, Japan

    Masahiko Hatano, Myeng Mo Kang & Takeshi Tokuhisa

  4. Chiba Cancer Center Research Institute, Chiba, Japan

    Shigeru Sakiyama

Authors
  1. Mitsuro Narita
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rumana Bahar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masahiko Hatano
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Myeng Mo Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takeshi Tokuhisa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shigemasa Goto
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hiromitsu Saisho
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Shigeru Sakiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Masatoshi Tagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masatoshi Tagawa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Narita, M., Bahar, R., Hatano, M. et al. Tissue-specific expression of a suicide gene for selective killing of neuroblastoma cells using a promoter region of the NCX gene. Cancer Gene Ther 8, 997–1002 (2001). https://doi.org/10.1038/sj.cgt.7700408

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.cgt.7700408

Keywords

This article is cited by

Search

Advanced search

Quick links