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Synthetic Tumor-Specific Promoters for Transcriptional Regulation of Viral Replication

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Mammalian Synthetic Promoters

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1651))

Abstract

Here we describe a collection of methods that have been adapted to isolate and modify tumor-specific promoters (TSPs) to drive viral replication for cancer therapy and other uses. We will describe as examples the secreted protein acidic and rich in cysteine (SPARC ) and the protease-activated receptor-1 (PAR-1) promoter. We outline strategies to select appropriate TSPs using bioinformatics resources and the methods utilized in their subsequent cloning, assessment of transcriptional activity, and their use in conditionally replicative oncolytic adenoviruses.

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References

  1. Xiong J, Sun WJ, Wang WF, Liao ZK, Zhou FX, Kong HY, Xu Y, Xie CH, Zhou YF (2012) Novel, chimeric, cancer-specific, and radiation-inducible gene promoters for suicide gene therapy of cancer. Cancer 118:536–548

    Article  CAS  Google Scholar 

  2. Viale DL, Cafferata EG, Gould D, Rotondaro C, Chernajovsky Y, Curiel DT, Podhajcer OL, Veronica Lopez M (2013) Therapeutic improvement of a stroma-targeted CRAd by incorporating motives responsive to melanoma microenvironment. J Invest Dermatol 133(11):2576–2584

    Article  CAS  Google Scholar 

  3. Hogg RT, Garcia JA, Gerard RD (2010) Adenoviral targeting of gene expression to tumors. Cancer Gene Ther 17:375–386

    Article  CAS  Google Scholar 

  4. Podhajcer OL, Benedetti L, Girotti MR, Prada F, Salvatierra E, Llera AS (2008) The role of the matricellular protein SPARC in the dynamic interaction between the tumor and the host. Cancer Metastasis Rev 27(3):523–537

    Article  CAS  Google Scholar 

  5. Lopez MV, Blanco P, Viale DL, Cafferata EG, Carbone C, Gould D, Chernajovsky Y, Podhajcer OL (2006) Expression of a suicidal gene under control of the human secreted protein acidic and rich in cysteine (SPARC ) promoter in tumor or stromal cells led to the inhibition of tumor cell growth. Mol Cancer Ther 5:2503–2511

    Google Scholar 

  6. 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:e5119

    Article  Google Scholar 

  7. 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(12):2222–2233

    Google Scholar 

  8. Tellez C, Bar-Eli M (2003) Role and regulation of the thrombin receptor (PAR-1) in human melanoma. Oncogene 22:3130–3137

    Article  CAS  Google Scholar 

  9. Arisato T, Sarker KP, Kawahara K, Nakata M, Hashiguchi T, Osame M, Kitajima I, Maruyama I (2003) The agonist of the protease-activated receptor-1 (PAR) but not PAR3 mimics thrombin-induced vascular endothelial growth factor release in human smooth muscle cells. Cell Mol Life Sci 60:1716–1724

    Article  CAS  Google Scholar 

  10. Yin YJ, Salah Z, Maoz M, Even Ram SC, Ochayon S, Neufeld G, Katzav S, Bar-Shavit R (2003) Oncogenic transformation induces tumor angiogenesis: a role for PAR1 activation. FASEB J 17:163–174

    Article  CAS  Google Scholar 

  11. Even-Ram S, Uziely B, Cohen P, Grisaru-Granovsky S, Maoz M, Ginzburg Y, Reich R, Vlodavsky I, Bar-Shavit R (1998) Thrombin receptor overexpression in malignant and physiological invasion processes. Nat Med 4:909–914

    Article  CAS  Google Scholar 

  12. Henrikson KP, Salazar SL, Fenton JW 2nd, Pentecost BT (1999) Role of thrombin receptor in breast cancer invasiveness. Br J Cancer 79:401–406

    Article  CAS  Google Scholar 

  13. Rudroff C, Schafberg H, Nowak G, Weinel R, Scheele J, Kaufmann R (1998) Characterization of functional thrombin receptors in human pancreatic tumor cells (MIA PACA-2). Pancreas 16:189–194

    Article  CAS  Google Scholar 

  14. Wojtukiewicz MZ, Tang DG, Ben-Josef E, Renaud C, Walz DA, Honn KV (1995) Solid tumor cells express functional “tethered ligand” thrombin receptor. Cancer Res 55:698–704

    CAS  PubMed  Google Scholar 

  15. Kaushal V, Kohli M, Dennis RA, Siegel ER, Chiles WW, Mukunyadzi P (2006) Thrombin receptor expression is upregulated in prostate cancer. Prostate 66:273–282

    Article  CAS  Google Scholar 

  16. Marshall O (2007) Graphical design of primers with PerlPrimer. Methods Mol Biol 402:403–414

    Article  CAS  Google Scholar 

  17. Dmitriev I, Krasnykh V, Miller CR, Wang M, Kashentseva E, Mikheeva G, Belousova N, Curiel DT (1998) An adenovirus vector with genetically modified fibers demonstrates expanded tropism via utilization of a coxsackievirus and adenovirus receptor-independent cell entry mechanism. J Virol 72:9706–9713

    Google Scholar 

  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 7:215–222

    Article  CAS  Google Scholar 

  19. Decker KB, Hinton DM (2013) Transcription regulation at the core: similarities among bacterial, archaeal, and eukaryotic RNA polymerases. Annu Rev Microbiol 67:113–139

    Article  CAS  Google Scholar 

  20. Arimbasseri AG, Rijal K, Maraia RJ (2014) Comparative overview of RNA polymerase II and III transcription cycles, with focus on RNA polymerase III termination and reinitiation. Transcription 5:e27639

    Article  Google Scholar 

  21. Juven-Gershon T, Kadonaga JT (2010) Regulation of gene expression via the core promoter and the basal transcriptional machinery. Dev Biol 339:225–229

    Article  CAS  Google Scholar 

  22. Dreos R, Ambrosini G, Perier RC, Bucher P (2015) The eukaryotic promoter database: expansion of EPDnew and new promoter analysis tools. Nucleic Acids Res 43:D92–D96

    Article  CAS  Google Scholar 

  23. Reese MG (2001) Application of a time-delay neural network to promoter annotation in the Drosophila melanogaster genome. Comput Chem 26:51–56

    Article  CAS  Google Scholar 

  24. Halees AS, Leyfer D, Weng Z (2003) PromoSer: a large-scale mammalian promoter and transcription start site identification service. Nucleic Acids Res 31:3554–3559

    Article  CAS  Google Scholar 

  25. Cartharius K, Frech K, Grote K, Klocke B, Haltmeier M, Klingenhoff A, Frisch M, Bayerlein M, Werner T (2005) MatInspector and beyond: promoter analysis based on transcription factor binding sites. Bioinformatics 21:2933–2942

    Article  CAS  Google Scholar 

  26. Chartier C, Degryse E, Gantzer M, Dieterle A, Pavirani A, Mehtali M (1996) Efficient generation of recombinant adenovirus vectors by homologous recombination in Escherichia coli. J Virol 70:4805–4810

    Google Scholar 

  27. Denizot F, Lang R (1986) Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods 89:271–277

    Article  CAS  Google Scholar 

  28. Jakubczak JL, Ryan P, Gorziglia M, Clarke L, Hawkins LK, Hay C, Huang Y, Kaloss M, Marinov A, Phipps S et al (2003) An oncolytic adenovirus selective for retinoblastoma tumor suppressor protein pathway-defective tumors: dependence on E1A, the E2F-1 promoter, and viral replication for selectivity and efficacy. Cancer Res 63:1490–1499

    Google Scholar 

  29. Martin-Duque P, Jezzard S, Kaftansis L, Vassaux G (2004) Direct comparison of the insulating properties of two genetic elements in an adenoviral vector containing two different expression cassettes. Hum Gene Ther 15:995–1002

    Article  CAS  Google Scholar 

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Correspondence to Maria Veronica Lopez .

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Lopez, M.V., Cafferata, E.G., Viale, D.L., Podhajcer, O.L. (2017). Synthetic Tumor-Specific Promoters for Transcriptional Regulation of Viral Replication. In: Gould, D. (eds) Mammalian Synthetic Promoters. Methods in Molecular Biology, vol 1651. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-7223-4_9

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  • DOI: https://doi.org/10.1007/978-1-4939-7223-4_9

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-7221-0

  • Online ISBN: 978-1-4939-7223-4

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