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Abstrakty
hTERT (human telomerase reverse transcriptase) plays a key role in the process of cell immortalization. Overexpression of hTERT has been implicated in 85% of malignant tumors and offers a specific target for cancer therapy. In this paper, we describe an effective approach using a single-chain variable fragment (scFv) intrabody derived from monoclonal hybridoma directed against hTERT to attenuate the immortalization of human uterine cervix and hepatoma cells. The scFv we constructed had a high affinity to hTERT, and specifically neutralized over 70% of telomere synthesis activity, thereby inhibiting the viability and proliferation of the cancer cells. Our results indicate that this anti-hTERT intrabody is a promising tool to target hTERT and intervene in the immortalization process of cancer cells.
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Czasopismo
Rocznik
Tom
Numer
Strony
32-45
Opis fizyczny
p.32-45,fig.,ref.
Bibliografia
- 1. Morin, G.B. The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats. Cell 3 (1989) 521-529.
- 2. Blackburn, E.H. Structure and function of telomeres. Nature 6319 (1991) 569-573.
- 3. Kim, N.W., Piatyszek, M.A., Prowse, K.R., Harley, C.B., West, M.D., Ho, P.L., Coviello, G.M., Wright, W.E., Weinrich, S.L. and Shay, J.W. Specific association of human telomerase activity with immortal cells and cancer. Science 5193 (1994) 2011-2015.
- 4. Meeker, A.K., Hicks, J.L., Platz, E.A., March, G.E., Bennett, C.J., Delannoy, M.J. and De Marzo, A.M. Telomere shortening is an early somatic DNA alteration in human prostate tumorigenesis. Cancer Res. 22 (2002) 6405-6409.
- 5. van Heek, N.T., Meeker, A.K., Kern, S.E., Yeo, C.J., Lillemoe, K.D., Cameron, J L., Offerhaus, G.J., Hicks, J.L., Wilentz, R.E., Goggins, M.G., De Marzo, A.M., Hruban, R.H. and Maitra, A. Telomere shortening is nearly universal in pancreatic intraepithelial neoplasia. Am. J. Pathol. 5 (2002) 1541-1547.
- 6. Meeker, A.K., Hicks, J.L., Gabrielson, E., Strauss, W.M., De Marzo, A.M. and Argani, P. Telomere shortening occurs in subsets of normal breast epithelium as well as in situ and invasive carcinoma. Am. J. Pathol. 3 (2004) 925-935.
- 7. Minev, B., Hipp, J., Firat, H1. Morin, G.B. The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats. Cell 3 (1989) 521-529.
- 2. Blackburn, E.H. Structure and function of telomeres. Nature 6319 (1991) 569-573.
- 3. Kim, N.W., Piatyszek, M.A., Prowse, K.R., Harley, C.B., West, M.D., Ho, P.L., Coviello, G.M., Wright, W.E., Weinrich, S.L. and Shay, J.W. Specific association of human telomerase activity with immortal cells and cancer. Science 5193 (1994) 2011-2015.
- 4. Meeker, A.K., Hicks, J.L., Platz, E.A., March, G.E., Bennett, C.J., Delannoy, M.J. and De Marzo, A.M. Telomere shortening is an early somatic DNA alteration in human prostate tumorigenesis. Cancer Res. 22 (2002) 6405-6409.
- 5. van Heek, N.T., Meeker, A.K., Kern, S.E., Yeo, C.J., Lillemoe, K.D., Cameron, J L., Offerhaus, G.J., Hicks, J.L., Wilentz, R.E., Goggins, M.G., De Marzo, A.M., Hruban, R.H. and Maitra, A. Telomere shortening is nearly universal in pancreatic intraepithelial neoplasia. Am. J. Pathol. 5 (2002) 1541-1547.
- 6. Meeker, A.K., Hicks, J.L., Gabrielson, E., Strauss, W.M., De Marzo, A.M. and Argani, P. Telomere shortening occurs in subsets of normal breast epithelium as well as in situ and invasive carcinoma. Am. J. Pathol. 3 (2004) 925-935.
- 7. Minev, B., Hipp, J., Firat, H., Schmidt, J.D., Langlade-Demoyen, P. and Zanetti, M. Cytotoxic T cell immunity against telomerase reverse transcriptase in humans. Proc. Natl. Acad. Sci. U.S.A. 9 (2000) 4796-4801.
- 8. Hytiroglou, P. and Theise, N.D. Telomerase activation in human hepatocarcinogenesis. Am. J. Gastroenterol. 4 (2006) 839-841.
- 9. Harrington, L., Zhou, W., McPhail, T., Oulton, R., Yeung, D.S., Mar, V., Bass, M.B. and Robinson, M.O. Human telomerase contains evolutionarily conserved catalytic and structural subunits. Genes Dev. 23 (1997) 3109-3115.
- 10. Weinrich, S.L., Pruzan, R., Ma, L., Ouellette, M., Tesmer, V.M., Holt, S.E., Bodnar, A.G., Lichtsteiner, S., Kim, N.W., Trager, J.B., Taylor, R.D., Carlos, R., Andrews, W.H., Wright, W.E., Shay, J.W., Harley, C.B. and Morin, G.B. Reconstitution of human telomerase with the template RNA component hTR and the catalytic protein subunit hTRT. Nat. Genet. 4 (1997) 498-502.
- 11. Vonderheide, R.H., Hahn, W.C., Schultze, J.L. and Nadler, L.M. The telomerase catalytic subunit is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes. Immunity 6 (1999) 673-679.
- 12. Meyerson, M., Counter, C.M., Eaton, E.N., Ellisen, L.W., Steiner, P., Caddle, S.D., Ziaugra, L., Beijersbergen, R.L., Davidoff, M.J., Liu, Q., Bacchetti, S., Haber, D.A. and Weinberg, R.A. hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization. Cell 4 (1997) 785-795.
- 13. Graessmann, A., Graessmann, M. and Mueller, C. Microinjection of early SV40 DNA fragments and T antigen. Methods Enzymol. 1 (1980) 816-825.
- 14. Morgan, D.O. and Roth, R.A. Analysis of intracellular protein function by antibody injection. Immunol. Today 3 (1988) 84-88.
- 15. Valle, G., Jones, E.A. and Colman, A. Anti-ovalbumin monoclonal antibodies interact with their antigen in internal membranes of Xenopus oocytes. Nature 5887 (1982) 71-74.
- 16. Burke, B. and Warren, G. Microinjection of mRNA coding for an anti-Golgi antibody inhibits intracellular transport of a viral membrane protein. Cell 4 (1984) 847-856.
- 17. Marasco, W.A. Intrabodies as antiviral agents. Curr. Top. Microbiol. Immunol. (2001) 247-270.
- 18. Marasco, W.A. Intrabodies: turning the humoral immune system outside in for intracellular immunization. Gene Ther. 1 (1997) 11-15.
- 19. Williams, B.R. and Zhu, Z. Intrabody-based approaches to cancer therapy: status and prospects. Curr. Med. Chem. 12 (2006) 1473-1480.
- 20. Biocca, S., Pierandrei-Amaldi, P. and Cattaneo, A. Intracellular expression of anti-p21ras single chain Fv fragments inhibits meiotic maturation of xenopus oocytes. Biochem. Biophys. Res. Commun. 2 (1993) 422-427.
- 21. Biocca, S., Pierandrei-Amaldi, P., Campioni, N. and Cattaneo, A. Intracellular immunization with cytosolic recombinant antibodies. Biotechnology (N. Y.) 4 (1994) 396-399.
- 22. Duan, L., Bagasra, O., Laughlin, M.A., Oakes, J.W. and Pomerantz, R.J. Potent inhibition of human immunodeficiency virus type 1 replication by an intracellular anti-Rev single-chain antibody. Proc. Natl. Acad. Sci. U.S.A. 11 (1994) 5075-5079.
- 23. Mhashilkar, A.M., Bagley, J., Chen, S.Y., Szilvay, A.M., Helland, D.G. and Marasco, W A. Inhibition of HIV-1 Tat-mediated LTR transactivation and HIV-1 infection by anti-Tat single chain intrabodies. EMBO J. 7 (1995) 1542-1551.
- 24. Marasco, W.A., Haseltine, W.A. and Chen, S.Y. Design, intracellular expression, and activity of a human anti-human immunodeficiency virus type 1 gp120 single-chain antibody. Proc. Natl. Acad. Sci. U.S.A. 16 (1993) 7889-7893.
- 25. Plumb, J.A., Bilsland, A., Kakani, R., Zhao, J., Glasspool, R.M., Knox, R.J., Evans, T.R. and Keith, W.N. Telomerase-specific suicide gene therapy vectors expressing bacterial nitroreductase sensitize human cancer cells to the pro-drug CB1954. Oncogene 53 (2001) 7797-7803.
- 26. Xiong, Y. and Eickbush, T.H. Origin and evolution of retroelements based upon their reverse transcriptase sequences. EMBO J. 10 (1990) 3353-3362.
- 27. Kalderon, D., Roberts, B.L., Richardson, W.D. and Smith, A.E. A short amino acid sequence able to specify nuclear location. Cell 3 Pt 2 (1984) 499-509.
- 28. Savre-Train, I., Gollahon, L.S. and Holt, S.E. Clonal heterogeneity in telomerase activity and telomere length in tumor-derived cell lines. Proc. Soc. Exp. Biol. Med. 4 (2000) 379-388.
- 29. Yang, N., Zhu, X., Chen, L., Li, S. and Ren, D. Oral administration of attenuated S. typhimurium carrying shRNA-expressing vectors as a cancer therapeutic. Cancer Biol. Ther. 1 (2008) 145-151.
- 30. Fu, W., Chu, L., Han, X., Liu, X. and Ren, D. Synergistic antitumoral effects of human telomerase reverse transcriptase-mediated dual-apoptosis-related gene vector delivered by orally attenuated Salmonella enterica Serovar Typhimurium in murine tumor models. J. Gene Med. 6 (2008) 690-701.
- 31. Strahl, C. and Blackburn, E.H. Effects of reverse transcriptase inhibitors on telomere length and telomerase activity in two immortalized human cell lines. Mol. Cell. Biol. 1 (1996) 53-65.
- 32. Seay, T.M., Peretsman, S.J. and Dixon, P.S. Inhibition of human transitional cell carcinoma in vitro proliferation by fluoroquinolone antibiotics. J. Urol. 2 (1996) 757-762.
- 33. Zhang, P.H., Zou, L. and Tu, Z.G. RNAi-hTERT inhibition hepatocellular carcinoma cell proliferation via decreasing telomerase activity. J. Surg. Res. 1 (2006) 143-149.
- 34. Holt, S.E., Aisner, D.L., Shay, J.W. and Wright, W.E. Lack of cell cycle regulation of telomerase activity in human cells. Proc. Natl. Acad. Sci. U.S.A. 20 (1997) 10687-10692.
- 35. Bonnin, E., Gruel, N., Moutel, S., Mantegazza, A.R., Barrio, M.M., Mordoh, J. and Teillaud, J.L. Generation of functional scFv intrabodies for triggering anti-tumor immunity. Methods 2 (2004) 225-232.
- 36. Cardinale, A., Lener, M., Messina, S., Cattaneo, A. and Biocca, S. The mode of action of Y13-259 scFv fragment intracellularly expressed in mammalian cells. FEBS Lett. 3 (1998) 197-202.
- 37. Strazisar, M., Mlakar, V. and Glavac, D. The expression of COX-2, hTERT, MDM2, LATS2 and S100A2 in different types of non-small cell lung cancer (NSCLC). Cell. Mol. Biol. Lett. 3 (2009) 442-456.
- 38. Harley, C.B. Telomere loss: mitotic clock or genetic time bomb? Mutat. Res. 2-6 (1991) 271-282.
- 39. Blackburn, E.H. Telomere states and cell fates. Nature 6808 (2000) 53-56.
- 40. Kelland, L.R. Overcoming the immortality of tumour cells by telomere and telomerase based cancer therapeutics-current status and future prospects. Eur. J. Cancer 7 (2005) 971-979.
- 41. Chang, J.T., Lu, Y.C., Chen, Y.J., Tseng, C.P., Chen, Y.L., Fang, C.W. and Cheng, A.J. hTERT phosphorylation by PKC is essential for telomerase holoprotein integrity and enzyme activity in head neck cancer cells. Br. J. Cancer 6 (2006) 870-878.
- 42. Wu, P., Meng, L., Wang, H., Zhou, J., Xu, G., Wang, S., Xi, L., Chen, G., Wang, B., Zhu, T., Lu, Y. and Ma, D. Role of hTERT in apoptosis of cervical cancer induced by histone deacetylase inhibitor. Biochem. Biophys. Res. Commun. 1 (2005) 36-44.
- 43. Ahmed, A. and Tollefsbol, T. Telomeres, telomerase, and telomerase inhibition: clinical implications for cancer. J. Am. Geriatr. Soc. 1 (2003) 116-122. ., Schmidt, J.D., Langlade-Demoyen, P. and Zanetti, M. Cytotoxic T cell immunity against telomerase reverse transcriptase in humans. Proc. Natl. Acad. Sci. U.S.A. 9 (2000) 4796-4801.
Typ dokumentu
Bibliografia
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bwmeta1.element.agro-article-ef47289e-ca82-4c97-b5e8-cdd1454bcc77