Advertisement

Application of Synthetic Tumor-Specific Promoters Responsive to the Tumor Microenvironment

  • Eduardo G. CafferataEmail author
  • Maria Veronica Lopez
  • Felipe J. Nuñez
  • Maria A. R. Maenza
  • Osvaldo L. Podhajcer
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1651)

Abstract

Activity of endogenous promoters can be altered by including additional responsive elements (REs). These elements can be responsive to features of the tumor environment or alternatively to signaling pathways specifically activated in cancer cells. These REs incorporated into tumor-specific promoters can improve cancer targeting, the replicative capacity, and lytic activity of conditionally replicative adenovirus. Here we outline an approach to incorporate hypoxia and inflammation REs into a specific fragment of the SPARC promoter and the steps to clone a nucleosome positioning sequence (NPS) identified in the osteocalcin promoter that contains a Wnt RE upstream of a heterologous synthetic promoter.

Key words

Synthetic tumor-specific promoter Hypoxia-responsive element Nuclear factor kappa B-responsive element Wnt-responsive element Nucleosome positioning sequence Adenovirus 

References

  1. 1.
    Martiniello-Wilks R, Garcia-Aragon J, Daja MM, Russell P, Both GW, Molloy PL, Lockett LJ, Russell PJ (1998) In vivo gene therapy for prostate cancer: preclinical evaluation of two different enzyme-directed prodrug therapy systems delivered by identical adenovirus vectors. Hum Gene Ther 9:1617–1626CrossRefGoogle Scholar
  2. 2.
    Onimaru M, Ohuchida K, Mizumoto K, Nagai E, Cui L, Toma H, Takayama K, Matsumoto K, Hashizume M, Tanaka M (2010) hTERT-promoter-dependent oncolytic adenovirus enhances the transduction and therapeutic efficacy of replication-defective adenovirus vectors in pancreatic cancer cells. Cancer Sci 101:735–742Google Scholar
  3. 3.
    Cafferata EG, Maccio DR, Lopez MV, Viale DL, Carbone C, Mazzolini G, Podhajcer OL (2009) A novel A33 promoter-based conditionally replicative adenovirus suppresses tumor growth and eradicates hepatic metastases in human colon cancer models. Clin Cancer Res 15:3037–3049CrossRefGoogle Scholar
  4. 4.
    Cao G, Kuriyama S, Gao J, Kikukawa M, Cui L, Nakatani T, Zhang X, Tsujinoue H, Pan X, Fukui H et al (1999) Effective and safe gene therapy for colorectal carcinoma using the cytosine deaminase gene directed by the carcinoembryonic antigen promoter. Gene Ther 6:83–90CrossRefGoogle Scholar
  5. 5.
    Osaki T, Tanio Y, Tachibana I, Hosoe S, Kumagai T, Kawase I, Oikawa S, Kishimoto T (1994) Gene therapy for carcinoembryonic antigen-producing human lung cancer cells by cell type-specific expression of herpes simplex virus thymidine kinase gene. Cancer Res 54:5258–5261PubMedGoogle Scholar
  6. 6.
    Ledda F, Bravo AI, Adris S, Bover L, Mordoh J, Podhajcer OL (1997) The expression of the secreted protein acidic and rich in cysteine (SPARC) is associated with the neoplastic progression of human melanoma. J Invest Dermatol 108:210–214Google Scholar
  7. 7.
    Framson PE, Sage EH (2004) SPARC and tumor growth: where the seed meets the soil? J Cell Biochem 92:679–690Google Scholar
  8. 8.
    Lopez MV, Rivera AA, Viale DL, Benedetti L, Cuneo N, Kimball KJ, Wang M, Douglas JT, Zhu ZB, Bravo AI et al (2012) A tumor-stroma targeted oncolytic adenovirus replicated in human ovary cancer samples and inhibited growth of disseminated solid tumors in mice. Mol Ther 20:2222–2233CrossRefGoogle Scholar
  9. 9.
    Powis G, Kirkpatrick L (2004) Hypoxia inducible factor-1alpha as a cancer drug target. Mol Cancer Ther 3:647–654PubMedGoogle Scholar
  10. 10.
    Cao Y, Linden P, Shima D, Browne F, Folkman J (1996) In vivo angiogenic activity and hypoxia induction of heterodimers of placenta growth factor/vascular endothelial growth factor. J Clin Invest 98:2507–2511CrossRefGoogle Scholar
  11. 11.
    Adriaansen J, Fallaux FJ, de Cortie CJ, Vervoordeldonk MJ, Tak PP (2007) Local delivery of beta interferon using an adeno-associated virus type 5 effectively inhibits adjuvant arthritis in rats. J Gen Virol 88:1717–1721CrossRefGoogle Scholar
  12. 12.
    Van Antwerp DJ, Martin SJ, Kafri T, Green DR, Verma IM (1996) Suppression of TNF-alpha-induced apoptosis by NF-kappaB. Science 274:787–789CrossRefGoogle Scholar
  13. 13.
    Blagodatski A, Poteryaev D, Katanaev VL (2014) Targeting the Wnt pathways for therapies. Mol Cell Ther 2:28Google Scholar
  14. 14.
    Song L, Li ZY, Liu WP, Zhao MR (2015) Crosstalk between Wnt/beta-catenin and Hedgehog/Gli signaling pathways in colon cancer and implications for therapy. Cancer Biol Ther 16:1–7Google Scholar
  15. 15.
    Bai L, Morozov AV (2010) Gene regulation by nucleosome positioning. Trends Genet 26:476–483CrossRefGoogle Scholar
  16. 16.
    Peckham HE, Thurman RE, Fu Y, Stamatoyannopoulos JA, Noble WS, Struhl K, Weng Z (2007) Nucleosome positioning signals in genomic DNA. Genome Res 17:1170–1177CrossRefGoogle Scholar
  17. 17.
    Lopez MV, Viale DL, Cafferata EG, Bravo AI, Carbone C, Gould D, Chernajovsky Y, Podhajcer OL (2009) Tumor associated stromal cells play a critical role on the outcome of the oncolytic efficacy of conditionally replicative adenoviruses. PLoS One 4:e5119CrossRefGoogle Scholar
  18. 18.
    Fallaux FJ, Kranenburg O, Cramer SJ, Houweling A, Van Ormondt H, Hoeben RC, Van Der Eb AJ (1996) Characterization of 911: a new helper cell line for the titration and propagation of early region 1-deleted adenoviral vectors. Hum Gene Ther 7:215–222CrossRefGoogle Scholar
  19. 19.
    Khoury M, Adriaansen J, Vervoordeldonk MJ, Gould D, Chernajovsky Y, Bigey P, Bloquel C, Scherman D, Tak PP, Jorgensen C et al (2007) Inflammation-inducible anti-TNF gene expression mediated by intra-articular injection of serotype 5 adeno-associated virus reduces arthritis. J Gene Med 9:596–604CrossRefGoogle Scholar
  20. 20.
    Subang MC, Fatah R, Bright C, Blanco P, Berenstein M, Wu Y, Podhajcer OL, Winyard PG, Chernajovsky Y, Gould D (2012) A novel hybrid promoter responsive to pathophysiological and pharmacological regulation. J Mol Med (Berl) 90:401–411CrossRefGoogle Scholar
  21. 21.
    Gutierrez J, Sierra J, Medina R, Puchi M, Imschenetzky M, van Wijnen A, Lian J, Stein G, Stein J, Montecino M (2000) Interaction of CBF alpha/AML/PEBP2 alpha transcription factors with nucleosomes containing promoter sequences requires flexibility in the translational positioning of the histone octamer and exposure of the CBF alpha site. Biochemistry 39:13565–13574CrossRefGoogle Scholar
  22. 22.
    Luo J, Deng ZL, Luo X, Tang N, Song WX, Chen J, Sharff KA, Luu HH, Haydon RC, Kinzler KW et al (2007) A protocol for rapid generation of recombinant adenoviruses using the AdEasy system. Nat Protoc 2:1236–1247CrossRefGoogle Scholar
  23. 23.
    Breyer B, Jiang W, Cheng H, Zhou L, Paul R, Feng T, He TC (2001) Adenoviral vector-mediated gene transfer for human gene therapy. Curr Gene Ther 1:149–162CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  • Eduardo G. Cafferata
    • 1
    Email author
  • Maria Veronica Lopez
    • 1
  • Felipe J. Nuñez
    • 1
  • Maria A. R. Maenza
    • 1
  • Osvaldo L. Podhajcer
    • 1
  1. 1.Laboratory of Molecular and Cellular TherapyLeloir Institute-CONICETBuenos AiresArgentina

Personalised recommendations