Abstract
Survivin is expressed in many cancers but not in normal adult tissues and is transcriptionally regulated. To test the feasibility of using the survivin promoter to induce cancer-specific transgene expression in lung cancer gene therapy, a vector expressing a luciferase gene driven by the survivin promoter was constructed and evaluated in vitro and in vivo. We found that the survivin promoter was generally more highly activated in cancer cell lines than in normal and immortalized normal cell lines. When delivered intravenously by DNA:liposome complexes, the survivin promoter was more than 200 times more cancer specific than the cytomegalovirus promoter in vivo. To identify lung cancer patients who may benefit from gene therapy with the survivin promoter, we measured survivin protein expression in surgical specimens of 75 non-small-cell lung cancers and 10 normal lung tissues by immunohistochemical staining and found that survivin is expressed in most of the non-small-cell lung cancers tested (81%, 61 of 75) but none of the normal lung tissues. The survivin promoter also induced transgene expression of a mutant Bik in cancer cells, which suppressed the growth of cancer cells in vitro and in vivo. These results indicate that the survivin promoter is a cancer-specific promoter for various cancers and that it may be useful in cancer gene therapy.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Parker SL, Tong T, Bolden S, Wingo PA . Cancer statistic, 1997. CA Cancer J Clin. 1997;47:5–27.
Templeton NS, Lasic DD, Frederik PM, et al. Improved DNA:liposome complexes for increased systemic delivery and gene expression. Nat Biotechnol. 1997;15:647–652.
Ramesh R, Saeki T, Templeton NS, et al. Successful treatment of primary and disseminated human lung cancers by systemic delivery of tumor suppressor genes using an improved liposome vector. Mol Therapy. 2001;3:337–350.
Gibbs JB . Mechanism based target identification and drug discovery in cancer research. Science. 2000;287:1969–1973.
Robertson MW, Wang M, Siegal GP, et al. Use of a tissue-specific promoter for targeted expression of the herpes simplex virus thymidine kinase gene in cervical carcinomal cells. Cancer Gene Ther. 1998;5:331–336.
Ambrosini G, Adida C, Altieri DC . A novel anti-apoptosis gene, Survivin, expressed in cancer and lymphoma. Nat Med. 1997;3:917–921.
Tamm I, Wang Y, Sausville E, et al. IAP-family protein Survivin inhibits caspase activity and apoptosis induced by Fas(CD95), Bax, caspases, and anticancer drugs. Cancer Res. 1998;58:5315–5320.
Altieri DC . The molecular basis and potential role of survivin in cancer diagnosis and therapy. Trends Mol Med. 2001;7:542–547.
Monzo M, Rosell R, Felip E, et al. A novel anti-apoptosis gene: re-expression of Survivin messenger RNA as a prognosis marker in non-small-cell lung cancers. J Clin Oncol. 1999;17:2100–2104.
Falleni M, Pellegrini C, Marchetti A, et al. Survivin gene expression in early-stage non-small cell lung cancer. J Pathol. 2003;200:620–626.
Tanaka K, Iwamoto S, Gon G, et al. Expression of survivin and its relationship to loss of apoptosis in breast carcinomas. Clin Cancer Res. 2000;6:127–134.
Kawasaki H, Altieri DC, Lu CD, et al. Inhibition of apoptosis by Survivin predicts shorter survival rates in colorectal cancer. Cancer Res. 1998;58:5071–5074.
Lu CD, Altieri DC, Tanigawa N . Expression of a novel anti-apoptosis gene, Survivin, correlated with tumor cell apoptosis and p53 accumulation in gastric carcinomas. Cancer Res. 1998;58:1808–1812.
Kato J, Kuwabara Y, Mitani M, et al. Expression of Survivin in esophageal cancer: correlation with the prognosis and response to chemotherapy. Int J Cancer. 2001;95:92–95.
Satoh K, Kaneko K, Hirota M, et al. Expression of Survivin is correlated with cancer cell apoptosis and is involved in the development of human pancreatic duct cell tumors. Cancer. 2001;92:271–278.
Swana HS, Grossman D, Anthony JN, et al. Tumor content of the anti-apoptosis molecule Survivin and recurrence of bladder cancer. New Engl J Med. 1999;341:452–453.
Saitoh Y, Yaginuma Y, Ishikawa M . Analysis of Bcl-2, Bax, and Survivin genes in uterine cancer. Int J Oncol. 1999;15:137–141.
Yoshida H, Ishiko O, Sumi T, et al. Survivin, Bcl-2 and matrix metalloproteinase-2 enhance progression of clear cell-and serous-type ovarian carcinomas. Int J Oncol. 2001;19:537–542.
Grossman D, McNiff JM, Li F, Altieri DC . Expression and targeting of the apoptosis inhibitor, Survivin, in human melanoma. J Invest Dermatol. 1999;113:1076–1081.
Adida C, Haioun C, Gaulard P, et al. Prognostic significance of Survivin expression in diffuse large B-cell lymphomas. Blood. 2000;96:1921–1925.
Adida C, Recher C, Raffoux E, et al. Expression and prognostic significance of Survivin in de novo acute myeloid leukemia. Br J Haematol. 2000;111:196–203.
Li F, Altieri DC . Transcriptional analysis of human survivin gene expression. Biochem J. 1999;344:305–311.
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.
Velculescu VE, Madden SL, Zhang L, et al. Analysis of human transcriptomes. Nat Genet. 1999;23:387–388.
Hofmann HS, Simm A, Hammer A, et al. Expression of inhibitors of apoptosis (IAP) proteins in non-small cell lung cancer. J Cancer Res Clin Oncol. 2002;128:554–560.
Olie RA, Simoes-Wust AP, Baumann B, et al. A novel antisense oligonucleotide targeting Survivin expression induces apoptosis and sensitizes lung cancer cells to chemotherapy. Cancer Res. 2000;60:2805–2809.
Mesri M, Wall NR, Li J, et al. Cancer gene therapy using a Survivin mutant adenovirus. J Clin Invest. 2001;108:981–990.
Altieri DC . Validating Survivin as a cancer therapeutic target. Nature Rev Cancer. 2003;3:46–54.
Adams JM, Cory S . The Bcl-2 protein family: arbiters of cell survival. Science. 1998;281:1322–1326.
Han J, Sabbatini P, White E . Induction of apoptosis by human Bbk/Bik, a BH3-containing protein that interacts with E1B 19 K. Mol Cell Biol. 1996;16:5857–5864.
Zou Y, Peng H, Zhou B, et al. Systemic tumor suppression by the proapoptotic gene Bik. Cancer Res. 2002;62:8–12.
Li YM, Wen Y, Ding QQ, Zhou BP, Hung MC . Enhancement of Bik anti-tumor effect by Bik mutants. Cancer Res. 2003;63:7630–7633.
Lee CM, Lo HW, Shao RP, et al. Selective activation of ceruloplasmin promoter in ovarian tumors: potential use for gene therapy. Cancer Res. 2004;64:1788–1793.
Cao H, Stamatoyannopoulos G, Jung M . Induction of human gamma globin gene expression by histone deacetylase inhibitors. Blood. 2004;103:701–709.
Kircheis R, Ostermann E, Wolschek MF, et al. Tumor-targeted gene delivery of tumor necrosis factor-α induces tumor necrosis and tumor regression without systemic toxicity. Cancer Gene Ther. 2002;9:673–680.
Tanyi JL, Lapushin R, Eder A, et al. Identification of tissue- and cancer-selective promoters for the introduction of genes into human ovarian cancer cells. Gynecol Oncol. 2002;85:451–458.
Acknowledgements
We thank Dr Stephanie A Miller for helpful discussions. This work was supported by Grants from SPORE in Ovarian Cancer P50CA83639 and SPORE in Pancreatic Cancer P20CA101936 (to M-C Hung). J-S Chen was also supported by a research grant from the National Science Council, Taiwan (NSC 92-2314-B-002-248). (CA 16672) MD Anderson supporting grant.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Chen, JS., Liu, JC., Shen, L. et al. Cancer-specific activation of the survivin promoter and its potential use in gene therapy. Cancer Gene Ther 11, 740–747 (2004). https://doi.org/10.1038/sj.cgt.7700752
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.cgt.7700752
Keywords
This article is cited by
-
Replicative conditioning of Herpes simplex type 1 virus by Survivin promoter, combined to ERBB2 retargeting, improves tumour cell-restricted oncolysis
Scientific Reports (2020)
-
A novel approach for assessment of prostate cancer aggressiveness using survivin-driven tumour-activatable minicircles
Gene Therapy (2019)
-
Use of the XRCC2 promoter for in vivo cancer diagnosis and therapy
Cell Death & Disease (2018)
-
Construction and characterization of gelonin and saporin plasmids for toxic gene-based cancer therapy
Archives of Pharmacal Research (2016)
-
Gene therapy with RNAi targeting UHRF1 driven by tumor-specific promoter inhibits tumor growth and enhances the sensitivity of chemotherapeutic drug in breast cancer in vitro and in vivo
Cancer Chemotherapy and Pharmacology (2012)