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:

Transcriptional targeting of tumors with a novel tumor-specific survivin promoter

Cancer Gene Therapy volume 11, pages 256–262 (2004)Cite this article

Abstract

It has been demonstrated that survivin, a novel member of the inhibitor of apoptosis (IAP) protein family, is expressed in human cancers but is undetectable in normal differentiated tissues. We employed a recombinant adenoviral vector (reAdGL3BSurvivin) in which a tumor-specific survivin promoter and a luciferase reporter gene were inserted into the E1-deleted region of adenovirus vector. Luciferase activity was measured in both multiple tumor cell lines and two primary melanoma cells infected with reAdGL3BSurvivin. Human fibroblast and mammary epithelial cell lines were used as negative controls. A reAdGL3CMV, containing the CMV promoter and luciferase gene, was used as a positive control to normalize the luciferase activity generated by the survivin promoter. Our data revealed that the survivin promoter showed high activity in both established tumor cell lines and the primary melanoma cells. In contrast, the in vivo studies indicated that the activities of survivin promoter were extremely low in the major mouse organs. The survivin promoter appears to be a promising tumor-specific promoter exhibiting a “tumor on” and “liver off” profile, and therefore, it may prove to be a good candidate for transcriptional targeting of cancer gene therapy in a wide variety of tumors.

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

Similar content being viewed by others

Abbreviations

bp:

base pairs

CMV:

cytomegalovirus

Cox-2:

cyclooxygenase 2

MOI:

multiplicity of infection

PFU:

plaque-forming units

vp:

viral particles

TSP:

tumor-specific promoter

References

  1. Casado E, Nettelbeck DM, Gomez-Navarro J, et al. Transcriptional targeting for ovarian cancer gene therapy. Gynecol Oncol. 2001;82:229–237.

    Article  CAS  PubMed  Google Scholar 

  2. Nettelbeck DM, Jerome V, Muller R . Gene therapy: designer promoters for tumour targeting. Trends Genet. 2000;16:174–181.

    Article  CAS  PubMed  Google Scholar 

  3. Quan S, Pan G, Lu C, et al. Experimental studies in vitro on the alpha-fetoprotein-specific promoter mediated target gene therapy of hepatocellular carcinoma. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 1999;21:111–117.

    CAS  PubMed  Google Scholar 

  4. Easty DJ, Bennett DC . Protein tyrosine kinases in malignant melanoma. Melanoma Res. 2000;10:401–411.

    Article  CAS  PubMed  Google Scholar 

  5. Lee SE, Jin RJ, Lee SG, et al. Development of a new plasmid vector with PSA-promoter and enhancer expressing tissue-specificity in prostate carcinoma cell lines. Anticancer Res. 2000;20:417–422.

    CAS  PubMed  Google Scholar 

  6. Yamamoto M, Alemany R, Adachi Y, et al. Characterization of the cyclooxygenase-2 promoter in an adenoviral vector and its application for the mitigation of toxicity in suicide gene therapy of gastrointestinal cancers. Mol Ther. 2001;3:385–394.

    Article  CAS  PubMed  Google Scholar 

  7. Adachi Y, Reynolds PN, Yamamoto M, et al. A midkine promoter-based conditionally replicative adenovirus for treatment of pediatric solid tumors and bone marrow tumor purging. Cancer Res. 2001;61:7882–7888.

    CAS  PubMed  Google Scholar 

  8. Zhu ZB, Makhija SK, Lu B, et al. Transcriptionally targeted recombinant adenoviral vector expression in tumors through the CXCR4 tumor specific promoter. Gene Therapy. 2003; (in press).

  9. Müller A, Homey B, Soto H, et al. Involvement of chemokine receptors in breast cancer metastasis. Nature. 2001;410:50–56.

    Article  PubMed  Google Scholar 

  10. Loetscher M, Geiser T, O'Reilly T, et al. Cloning of a human seven-transmembrane domain receptor, LESTR, that is highly expressed in leukocytes. J Biol Chem. 1994;269:232–237.

    CAS  PubMed  Google Scholar 

  11. Bleul CC, Farzan M, Choe H, et al. The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature. 1996;382:829–833.

    Article  CAS  PubMed  Google Scholar 

  12. D'Apuzzo M, Rolink A, Loetscher M, et al. The chemokine SDF-1, stromal cell-derived factor 1, attracts early stage B cell precursors via the chemokine receptor CXCR4. Eur J Immunol. 1997;27:1788–1793.

    Article  CAS  PubMed  Google Scholar 

  13. Ayehunie S, Garcia-Zepeda EA, Hoxie JA, et al. Human immunodeficiency virus-1 entry into purified blood dendritic cells through CC and CXC chemokine coreceptors. Blood. 1997;90:1379–1386.

    CAS  PubMed  Google Scholar 

  14. Altieri DC . Xa receptor EPR-1. FASEB J. 1995;9:860–865.

    Article  CAS  PubMed  Google Scholar 

  15. Uren AG, Pakusch M, Hawkins CJ, et al. Cloning and expression of apoptosis inhibitory protein homologs that function to inhibit apoptosis and/or bind tumor necrosis factor receptor-associated factors. Proc Natl Acad Sci USA. 1996;93:4974–4978.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Takahashi R, Deveraux Q, Tamm I, et al. A single BIR domain of XIAP sufficient for inhibiting caspases. J Biol Chem. 1998;273:7787–7790.

    Article  CAS  PubMed  Google Scholar 

  17. Duckett CS, Nava VE, Gedrich RW, et al. A conserved family of cellular genes related to the baculovirus IAP gene and encoding apoptosis inhibitors. EMBO J. 1996;15:2685–2694.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ambrosini G, Adida C, Altieri DC . A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med. 1997;3:917–921.

    Article  CAS  PubMed  Google Scholar 

  19. Adida C, Crotty PL, McGrath J, et al. Developmentally regulated expression of the novel cancer anti-apoptosis gene survivin in human and mouse differentiation. Am J Pathol. 1998;152:43–49.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Bao R, Connolly DC, Murphy M, et al. Activation of cancer-specific gene expression by the survivin promoter. J Natl Cancer Inst. 2002;94:522–528.

    Article  CAS  PubMed  Google Scholar 

  21. Nasu S, Yagihashi A, Izawa A, et al. Survivin mRNA expression in patients with breast cancer. Anticancer Res. 2002;22:1839–1843.

    CAS  PubMed  Google Scholar 

  22. Sarela AI, Verbeke CS, Ramsdale J, et al. Expression of survivin, a novel inhibitor of apoptosis and cell cycle regulatory protein, in pancreatic adenocarcinoma. Br J Cancer. 2002;86:886–889.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ikeguchi M, Kaibara N . survivin messenger RNA expression is a good prognostic biomarker for oesophageal carcinoma. Br J Cancer. 2002;87:883–887.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Das A, Tan WL, Teo J, Smith DR . Expression of survivin in primary glioblastomas. J Cancer Res Clin Oncol. 2002;128:302–306.

    Article  CAS  PubMed  Google Scholar 

  25. Zaffaroni N, Pennati M, Colella G, et al. Expression of the anti-apoptotic gene survivin correlates with taxol resistance in human ovarian cancer. Cell Mol Life Sci. 2002;59:1406–1412.

    Article  CAS  PubMed  Google Scholar 

  26. He TC, Zhou S, da Costa LT, et al. A simplified system for generating recombinant adenoviruses. Proc Natl Acad Sci USA. 1998;95:2509–2514.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Li F, Altieri DC . Transcriptional analysis of human survivin gene expression. Biochem J. 1999;344 Part 2:305–311.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Chakravarti A, Noll E, Black PM, et al. Quantitatively determined survivin expression levels are of prognostic value in human gliomas. J Clin Oncol. 2002;20:1063–1068.

    Article  CAS  PubMed  Google Scholar 

  29. Li F . Survivin study: what is the next wave. Journal of CellularPhysiology. 2003;197:8–29.

    CAS  Google Scholar 

  30. Asanuma K, Kobayashi D, Furuya D, et al. A role for survivin in radioresistance of pancreatic cancer cells. Jpn J Cancer Res. 2002;93:1057–1062.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Altieri DC . Validating survivin as a cancer therapeutic target. Nat Rev Cancer. 2003;3:46–54.

    Article  CAS  PubMed  Google Scholar 

  32. Ambrosini G, Adida C, Sirugo G, et al. Induction of apoptosis and inhibition of cell proliferation by survivin gene targeting. J Biol Chem. 1998;273:11177–11182.

    Article  CAS  PubMed  Google Scholar 

  33. Tamm I, Wang Y, Sausville E, et al. IAP-family proteinsurvivin inhibits caspase activity and apoptosis induced by Fas (CD59), Bax, caspases, and anticancerdrugs. Cancer Res. 1998;58:5315–5320.

    CAS  PubMed  Google Scholar 

  34. Yamamoto T, Manome Y, Nakamura M, et al. Downregulation of survivin expression by induction of the effector cell protease receptor-1 reduces tumor growth potential and results in an increased sensitivity to anticancer agents in human colon cancer. Eur J Cancer. 2002;38:2316–2324.

    Article  CAS  PubMed  Google Scholar 

  35. Andersen MH, Pedersen LO, Becker JC, et al. Identification of a cytotoxic T lymphocyte response to the apoptosis inhibitor protein survivin in cancer patients. Cancer Res. 2001;61:869–872.

    CAS  PubMed  Google Scholar 

  36. van der Eb MM, Cramer SJ, Vergouwe Y, et al. Severe hepatic dysfunction after adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene and ganciclovir administration. Gene Ther. 1998;5:451–458.

    Article  CAS  PubMed  Google Scholar 

  37. Alvarez RD, Barnes MN, Gomez-Navarro J, et al. A cancer gene therapy approach utilizing an anti-erbB-2 single-chain antibody-encoding adenovirus (AD21): a phase I trial. Clin Cancer Res. 2000;6:3081–3087.

    CAS  PubMed  Google Scholar 

  38. Nettelbeck DM, Rivera AA, Davydova RJ, et al. Cox2 promoter for tumor-specific targeting for adenovirual vector to melanoma. Melanoma Res. 2003;13:287–292.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by research grants from the National Institutes of Health: R01 CA83821, R01 HL67962, K12 HD01261-02 (WRHR) 5P50 CA83591 (Ovarian SPORE Developmental Grant.

We thank Dr Suresh Boppana for the control cell line, HFBC, and Dr D Dieckmann for two primary melanoma cells.

Author information

Authors and Affiliations

  1. Division of Human Gene Therapy, Department of Medicine, Pathology, and The Gene Therapy Center, University of Alabama at Birmingham, Birmingham, AL, USA

    Zeng B Zhu, Baogen Lu, Lioudmila Kaliberova, Bin Liu, Angel A Rivera, Dirk M Nettelbeck, Parameshwar J Mahasreshti, Shannon Barker, Masato Yamaoto & David T Curiel

  2. Division of Gynecologic Oncology, University of Alabama at Birmingham, Birmingham, AL, USA

    Sharmila K Makhija, Minghui Wang, Charles A Leath III & Ronald D Alvarez

  3. Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA

    Fengzhi Li

Authors
  1. Zeng B Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sharmila K Makhija
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Baogen Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Minghui Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lioudmila Kaliberova
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Angel A Rivera
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Dirk M Nettelbeck
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Parameshwar J Mahasreshti
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Charles A Leath III
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Shannon Barker
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Masato Yamaoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Fengzhi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Ronald D Alvarez
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. David T Curiel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David T Curiel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhu, Z., Makhija, S., Lu, B. et al. Transcriptional targeting of tumors with a novel tumor-specific survivin promoter. Cancer Gene Ther 11, 256–262 (2004). https://doi.org/10.1038/sj.cgt.7700679

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.cgt.7700679

Keywords

This article is cited by

Search

Advanced search

Quick links