Skip to main content

Advertisement

SpringerLink
Log in

Experimental animal model and RNA interference: a promising association for bladder cancer research

  • Review
  • Published:
World Journal of Urology Aims and scope Submit manuscript

Abstract

Animal models are at the centre of laboratory bladder cancer (BC) research and at the same time, the bridge to the clinic. A new and very promising therapeutical approach is to silence abnormally up-regulated genes in cancer, through small interfering RNA (siRNA) molecules. Therapeutic use and success of siRNAs will largely depend on their efficient and safe in vivo delivery and on avoiding accidental off-target effects. Intravesical siRNA is a strategy which may be the best deliver option to surperficial BC like intravesical immunotherapy. Its direct action might allow a continuous intracellular exposure to effective siRNA concentrations. While the procedure of transurethral siRNA administration is promising for BC research allowing detection of new targets in BC therapy, the optimal intravesical carrier and the best target(s) to siRNA are to be determined.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. The American Cancer Society (2008) Overview: bladder cancer. In: How many people get bladder cancer? American Cancer Society, Atlanta. Available via ACS. http://www.cancer.org/docroot/CRI/content/CRI_2_2_1X_How_many_people_get_bladder_cancer_44.asp?sitearea. Cited 11 Sep 2008

  2. Kroft SH, Oyasu R (1994) Urinary bladder cancer: mechanisms of development and progression. Lab Invest 71:158–174

    PubMed  CAS  Google Scholar 

  3. Zeegers MP, Tan FE, Dorant E et al (2000) The impact of characteristics of cigarette smoking on urinary tract cancer risk: a meta-analysis of epidemiologic studies. Cancer 89:630–639

    Article  PubMed  CAS  Google Scholar 

  4. Granella M, Priante E, Nardini B, Bono R et al (1996) Excretion of mutagens, nicotine and its metabolites in urine of cigarette smokers. Mutagenesis 11:207–211

    Article  PubMed  CAS  Google Scholar 

  5. Grimmer G, Dettbarn G, Seidel A et al (2000) Detection of carcinogenic aromatic amines in the urine of non-smokers. Sci Total Environ 247:81–90

    Article  PubMed  CAS  Google Scholar 

  6. Zhang ZT, Pak J, Huang HY et al (2001) Role of Ha-ras activation in superficial papillary pathway of urothelial tumor formation. Oncogene 20:1973–1980

    Article  PubMed  CAS  Google Scholar 

  7. Zhang ZT, Pak J, Shapiro E, Sun TT, Wu XR (1999) Urothelium-specific expression of an oncogene in transgenic mice induced carcinoma in situ and invasive transitional cell carcinoma. Cancer Res 59:3512–3517

    PubMed  CAS  Google Scholar 

  8. Johnson AM, Conover DL, Huang J, Messing EM, Ning R, O’Connell MJ, Rossi MA, Sun TT, Wood RW, Wu XR, Reeder JE (2006) Early detection and measurement of urothelial tumors in mice. Urology 67:1309–1314

    Article  PubMed  Google Scholar 

  9. Hicks RM (1980) Multistage carcinogenesis in the urinary bladder. Br Med Bull 36:39–46

    PubMed  CAS  Google Scholar 

  10. Owens DM, Wei S, Smart RC (1999) A multihit, multistage model of chemical carcinogenesis. Carcinogenesis 20:1837–1844

    Article  PubMed  CAS  Google Scholar 

  11. Oliveira PA, Colaco A, De la Cruz PLF et al (2006) Experimental bladder carcinogenesis-rodent models. Exp Oncol 28:2–11

    PubMed  CAS  Google Scholar 

  12. Yao R, Lemon WJ, Wang Y et al (2004) Altered gene expression profile in mouse bladder cancers induced by hydroxybutyl(butyl) nitrosamine. Neoplasia 6:569–577

    Article  PubMed  CAS  Google Scholar 

  13. Oyasu R (1995) Epithelial tumours of the lower urinary tract in humans and rodents. Food Chem Toxicol 33:747–755

    Article  PubMed  CAS  Google Scholar 

  14. Williams PD, Lee JK, Theodorescu D (2008) Molecular credentialing of rodent bladder carcinogenesis models. Neoplasia 10(8):838–846

    PubMed  CAS  Google Scholar 

  15. Cohen SM (2002) Comparative pathology of proliferative lesions of the urinary bladder. Toxicol Pathol 30:663–671

    Article  PubMed  CAS  Google Scholar 

  16. Fukushima S, Friedell GH, Jacobs JB et al (1981) Effect of l-tryptophan and sodium saccharin on urinary tract carcinogenesis initiated by N-[4-(5-nitro–2-furyl)-2-thiazolyl] formamide. Cancer Res 41:3100–3103

    PubMed  CAS  Google Scholar 

  17. Epstein JI, Amin MB, Reuter VR et al (1998) The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Bladder Consensus Conference Committee. Am J Surg Pathol 22:1435–1448

    Article  PubMed  CAS  Google Scholar 

  18. Raghavan D, Debruyne F, Herr H (1986) Experimental models of bladder cancer: a critical review. In: Alan R et al (eds) Developments in bladder cancer. Liss, Inc., New York, pp 171–208

    Google Scholar 

  19. Marceau N (1990) Cell lineages and differentiation programs in epidermal, urothelial and hepatic tissues and their neoplasms. Lab Invest 63:4–20

    PubMed  CAS  Google Scholar 

  20. Limas C, Bair R, Bernhart P et al (1993) Proliferative activity of normal and neoplastic urothelium and its relation to epidermal growth factor and transferrin receptors. J Clin Pathol 46:810–816

    Article  PubMed  CAS  Google Scholar 

  21. Stewart FA (1986) Mechanism of bladder damage and repair after treatment with radiation and cytostatic drugs. Br J Cancer Suppl 7:280–291

    PubMed  CAS  Google Scholar 

  22. Crallan RA, Georgopoulos NT, Sothgate J (2006) Experimental models of human bladder carcinogenesis. Carcinogenesis 27:374–381

    Article  PubMed  CAS  Google Scholar 

  23. Hicks RM, Wakefield JS (1972) Rapid induction of bladder cancer in rats with N-methyl-N-nitrosourea. I. Histology. Chem Biol Interact 5:139–152

    Article  PubMed  CAS  Google Scholar 

  24. Kunze E, Graewe T, Scherber S et al (1989) Cell cycle dependence of N-methyl-N-nitrosourea-induced tumour development in the proliferating, partially resected rat urinary bladder. Br J Exp Pathol 70:125–142

    PubMed  CAS  Google Scholar 

  25. Magee PN, Barnes JM (1967) Carcinogenic nitroso compounds. Adv Cancer Res 10:163–246

    Article  PubMed  CAS  Google Scholar 

  26. Steinberg GD, Brendler CB, Ichikawa T et al (1990) Characterization of an N-methyl-N-nitrosourea induced autochthonous rat bladder cancer model. Cancer Res 50:6668–6741

    PubMed  CAS  Google Scholar 

  27. Gunther JH, Jurczok A, Wulf T et al (1999) Optimizing syngeneic orthotopic murine bladder cancer (MB49). Cancer Res 59:2834–2837

    PubMed  CAS  Google Scholar 

  28. Steinberg GD, Brendler CB, Squire RA et al (1991) Experimental intravesical therapy for superficial transitional cell carcinoma in a rat bladder tumor model. J Urol 145:647–653

    PubMed  CAS  Google Scholar 

  29. Grippo PJ, Sandgren EP (2005) Modeling pancreatic cancer in animals to address specific hypothesis. Methods Mol Med 103:217–243

    PubMed  CAS  Google Scholar 

  30. Gollapudi BB, Stott WT, Yano BL, Bus JS (1998) Mode of action considerations in the use of transgenic animals for mutagenicity and carcinogenicity evaluations. Toxicol Lett 103:479–484

    Article  Google Scholar 

  31. Lin JH, Zhao H, Sun TT (1995) A tissue-specific promoter that can drive a foreign gene to express in the suprabasal urothelial cells of transgenic mice. Proc Natl Acad Sci USA 9:679–683

    Article  Google Scholar 

  32. Kerr DE, Liang F, Bondioli KR, Zhao H, Kreibich G, Wall RJ, Sun TT (1998) The bladder as a bioreactor: urothelium production and secretion of growth hormone into urine. Nat Biotechnol 16:75–79

    Article  PubMed  CAS  Google Scholar 

  33. McNanley AR, Johnson AM, Flynn MK, Wood RW, Kennedy SD, Reeder JE (2009) Inherited pelvic organ prolapse in the mouse: preliminary evaluation of a new murine model. Int Urogynecol J Pelvic Floor Dysfunct 20:19–25

    PubMed  Google Scholar 

  34. Reznikoff CA, Sarkar S, Julicher KP, Burger MS, Puthenveettil JA, Jarrard DF et al (2000) Genetic alterations and biological pathways in human bladder cancer pathogenesis. Urol Oncol 5:191–203

    Article  PubMed  CAS  Google Scholar 

  35. Bex A, Vooijs M, Horenblas S, Berns A (2002) Controlling gene expression in the urothelium using transgenic mice with inducible bladder specific CRE-LOX recombination. J Urol 168:2641–2644

    Article  PubMed  CAS  Google Scholar 

  36. Spruck CH III, Ohneseit PF, Gonzalez-Zulueta M, Esrig D, Miyao N, Tsai YC et al (1994) Two molecular pathways to transitional cell carcinoma of the bladder. Cancer Res 54:784–788

    PubMed  CAS  Google Scholar 

  37. Akagi K, Sandig V, Vooijs M, van der Valk M, Giovannini M, Strauss M et al (1997) Cre-mediated somatic site-specific recombination in mice. Nucleic Acids Res 25:1766–1773

    Article  PubMed  CAS  Google Scholar 

  38. Saam JR, Gordon JI (1999) Inducible gene knockouts in small intestinal and colonic epithelium. J Biol Chem 274:38071–38082

    Article  PubMed  CAS  Google Scholar 

  39. Shibata H, Toyama K, Shioya H, Ito M, Hirota M, Hasegawa S et al (1997) Rapid colorectal adenoma formation initiated by conditional targeting of the Apc gene. Science 278:120–123

    Article  PubMed  CAS  Google Scholar 

  40. Chong L, Ruping Y, Jiancheng B, Guohong Y, Yougang F, Jiansong W et al (2006) Characterization of a novel transplantable orthotopic murine xenograft model of a human bladder transitional cell tumor (BIU-87). Cancer Biol Ther 5:394–398

    Article  PubMed  Google Scholar 

  41. Kubota T (1994) Metastatic models of human cancer xenografted in the nude mouse: the importance of orthotopic transplantation. J Cell Biochem 56:4–8

    Article  PubMed  CAS  Google Scholar 

  42. Cohen SM, Friedell GH (1982) The mouse in biomedical research. In: Neoplasms of the urinary system, chap. 24, Academic, New York, pp 439–463

  43. Reynolds A, Leake D, Boese Q et al (2004) Rational siRNA design for RNA interference. Nat Biotechnol 22:326–330

    Article  PubMed  CAS  Google Scholar 

  44. White MD, Farmer M, Mirabile I et al (2008) Single treatment with RNAi against prion protein rescues early neuronal dysfunction and prolongs survival in mice with prion disease. Proc Natl Acad Sci USA 105:10238–10243

    Article  PubMed  CAS  Google Scholar 

  45. Li BJ, Tang Q, Cheng D et al (2005) Using siRNA in prophylactic and therapeutic regimens against SARS coronavirus in Rhesus macaque. Nat Med 11:944–951

    PubMed  CAS  Google Scholar 

  46. Kuijl C, Savage ND, Marsman M et al (2007) Intracellular bacterial growth is controlled by a kinase network around PKB/AKT1. Nature 450:725–730

    Article  PubMed  CAS  Google Scholar 

  47. Pereira TC, Pascoal VD, Marchesini RB et al (2008) Schistosoma mansoni: evaluation of an RNAi-based treatment targeting HGPRTase gene. Exp Parasitol 118:619–623

    Article  PubMed  CAS  Google Scholar 

  48. DiFiglia M, Sena-Esteves M, Chase K et al (2007) Therapeutic silencing of mutant huntingtin with siRNA attenuates striatal and cortical neuropathology and behavioral deficits. Proc Natl Acad Sci USA 104:17204–17209

    Article  PubMed  CAS  Google Scholar 

  49. Taniguchi E, Nishijo K, McCleish AT et al (2008) PDGFR-A is a therapeutic target in alveolar rhabdomyosarcoma. Oncogene. doi:10.1038/onc.2008.255

  50. Bessard A, Frémin C, Ezan F et al (2008) RNAi-mediated ERK2 knockdown inhibits growth of tumor cells in vitro and in vivo. Oncogene 27:5315–5325

    Article  PubMed  CAS  Google Scholar 

  51. Zheng JN, Ma TX, Cao JY et al (2006) Knockdown of Ki-67 by small interfering RNA leads to inhibition of proliferation and induction of apoptosis in human renal carcinoma cells. Life Sci 78:724–729

    Article  PubMed  CAS  Google Scholar 

  52. Zamore PD (2006) RNA interference: big applause for silencing in Stockholm. Cell 127:1083–1086

    Article  PubMed  CAS  Google Scholar 

  53. Zhao W, Xu Y, Kong D et al (2008) Tissue-selective RNA interference in prostate cancer cell using prostate specific membrane antigen promoter/enhancer. Urol Oncol doi:10.1016/j.urolonc.2008.05.003

  54. Golshani R, Lopez L, Estrella V, Kramer M, Iida N, Lokeshwar VB (2008) Hyaluronic acid synthase-1 expression regulates bladder cancer growth, invasion, and angiogenesis through CD44. Cancer Res 68:483–491

    Article  PubMed  CAS  Google Scholar 

  55. Teng J, Wang ZY, Jarrard DF, Bjorling DE (2008) Roles of estrogen receptor alpha and beta in modulating urothelial cell proliferation. Endocr Relat Cancer 15:351–364

    Article  PubMed  CAS  Google Scholar 

  56. Stettner M, Kaulfuss S, Burfeind P, Schweyer S, Strauss A, Ringert RH, Thelen P (2007) The relevance of estrogen receptor-beta expression to the antiproliferative effects observed with histone deacetylase inhibitors and phytoestrogens in prostate cancer treatment. Mol Cancer Ther 6:2626–2633

    Article  PubMed  CAS  Google Scholar 

  57. Dong Z, Saliganan AD, Meng H et al (2008) Prostate cancer cell-derived urokinase-type plasminogen activator contributes to intraosseous tumor growth and bone turnover. Neoplasia 10:439–449

    PubMed  CAS  Google Scholar 

  58. Najy AJ, Day KC, Day ML (2008) ADAM15 supports prostate cancer metastasis by modulating tumor cell-endothelial cell interaction. Cancer Res 68:1092–1099

    Article  PubMed  CAS  Google Scholar 

  59. Aoki H, Satoh M, Mitsuzuka K et al (2004) Inhibition of motility and invasiveness of renal cell carcinoma induced by short interfering RNA transfection of beta 1, 4GalNAc transferase. FEBS Lett 567:203–208

    Article  PubMed  CAS  Google Scholar 

  60. Boorjian S, Heemers H, Frank I, Farmer S, Schmidt L, Sebo T, Tindall D (2008) Expression and significance of androgen receptor coactivators in urothelial carcinoma of the bladder. Endocr Relat Cancer (Epub ahead of print)

  61. Hara T, Miyazaki H, Lee A, Tran CP, Reiter RE (2008) Androgen receptor and invasion in prostate cancer. Cancer Res 68:1128–1135

    Article  PubMed  CAS  Google Scholar 

  62. Greenberg DA, Jin K (2005) From angiogenesis to neuropathology. Nature 438:954–959

    Article  PubMed  CAS  Google Scholar 

  63. Shinojima T, Oya M, Takayanagi A et al (2007) Renal cancer cells lacking hypoxia inducible factor (HIF)-1alpha expression maintain vascular endothelial growth factor expression through HIF-2alpha. Carcinogenesis 28:529–536

    Article  PubMed  CAS  Google Scholar 

  64. Fuessel S, Herrmann J, Ning S et al (2006) Chemosensitization of bladder cancer cells by survivin-directed antisense oligodeoxynucleotides and siRNA. Cancer Lett 232:243–254

    Article  PubMed  CAS  Google Scholar 

  65. Aigner A (2006) Gene silencing through RNA interference (RNAi) in vivo: strategies based on the direct application of siRNAs. J Biotechnol 124:12–25

    Article  PubMed  CAS  Google Scholar 

  66. Aigner A (2006) Delivery systems for the direct application of siRNAs to induce RNA interference (RNAi) in vivo. J Biomed Biotechnol. doi:10.1155/JBB/2006/71659

  67. Hacein-Bey-Abina S, von Kalle C, Schmidt M et al (2003) A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N Engl J Med 348:255–256

    Article  PubMed  Google Scholar 

  68. Sioud M, Sorensen DR (2003) Cationic liposome-mediated delivery of siRNAs in adult mice. Biochem Biophys Res Commun 312:1220–1225

    Article  PubMed  CAS  Google Scholar 

  69. Sorensen DR, Leirdal M, Sioud M (2003) Gene silencing by systemic delivery of synthetic siRNAs in adult mice. J Mol Biol 327:761–766

    Article  PubMed  CAS  Google Scholar 

  70. Nogawa M, Yuasa T, Kimura S et al (2005) Intravesical administration of small interfering RNA targeting PLK-1 successfully prevents the growth of bladder cancer. J Clin Invest 115:978–985

    PubMed  CAS  Google Scholar 

  71. Aigner A (2007) Applications of RNA interference: current state and prospects for siRNA-based strategies in vivo. Appl Microbiol Biotechnol 76:9–21

    Article  PubMed  CAS  Google Scholar 

  72. Hadaschik BA, Jackson J, Fazli L et al (2008) Intravesically administered antisense oligonucleotides targeting heat-shock protein-27 inhibit the growth of non-muscle-invasive bladder cancer. BJU Int 102:610–616

    Article  PubMed  CAS  Google Scholar 

  73. Jackson AL, Bartz SR, Schelter J et al (2003) Expression profiling reveals off-target gene regulation by RNAi. Nat Biotechnol 21:635–637

    Article  PubMed  CAS  Google Scholar 

  74. Lander ES, Linton LM, Birren B et al (2001) International Human Genome Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature 409:860–921

    Article  PubMed  CAS  Google Scholar 

  75. Pereira TC, Pascoal VDB, Secolin R et al (2007) Strand Analysis, a free online program for the computational identification of the best RNA interference (RNAi) targets based on Gibbs free energy. Genet Mol Biol 30:1206–1208

    Article  CAS  Google Scholar 

  76. Kumar P, Wu H, McBride JL et al (2007) Transvascular delivery of small interfering RNA to the central nervous system. Nature 448:39–43

    Article  PubMed  CAS  Google Scholar 

  77. Mullighan CG, Goorha S, Radtke I et al (2007) Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature 446:758–764

    Article  PubMed  CAS  Google Scholar 

  78. Greenman C, Stephens P, Smith R et al (2007) Patterns of somatic mutation in human cancer genomes. Nature 446:153–158

    Article  PubMed  CAS  Google Scholar 

  79. Fuessel S, Meye A, Kraemer K et al (2007) Synthetic nucleic acids as potential therapeutic tools for treatment of bladder carcinoma. Eur Urol 51:315–326

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest statement

There is no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Urology, Faculty of Medical Sciences, University of Campinas, UNICAMP, R. Votorantim, 51, ap. 43, Campinas, Sao Paulo, 13073-090, Brazil

    Leonardo Oliveira Reis & Ubirajara Ferreira

  2. Department of Medical Genetics, Faculty of Medical Sciences, University of Campinas, UNICAMP, Campinas, Brazil

    Tiago Campos Pereira & Iscia Lopes-Cendes

  3. Department of Anatomy, Institute of Biology, University of Campinas, UNICAMP, Campinas, Brazil

    Wagner José Favaro & Valéria Helena Alves Cagnon

Authors
  1. Leonardo Oliveira Reis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tiago Campos Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wagner José Favaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Valéria Helena Alves Cagnon
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Iscia Lopes-Cendes
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ubirajara Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Leonardo Oliveira Reis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reis, L.O., Pereira, T.C., Favaro, W.J. et al. Experimental animal model and RNA interference: a promising association for bladder cancer research. World J Urol 27, 353–361 (2009). https://doi.org/10.1007/s00345-009-0374-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00345-009-0374-4

Keywords

Search

Navigation