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Journal of Oncology
Volume 2012 (2012), Article ID 278312, 11 pages
http://dx.doi.org/10.1155/2012/278312
Review Article

Molecular Mechanism and Potential Targets for Blocking HPV-Induced Lesion Development

1Division of Chronic Infections and Cancer, Research Center for Infectious Diseases, Instituto Nacional de Salud Pública, Avenida Universidad No. 655, Cuernavaca 62100, Morelos, Mexico
2Universidad Politécnica del Estado de Morelos, Boulevard Cuauhnáhuac 566, Jiutepec 62550, Morelos, Mexico

Received 30 July 2011; Revised 27 September 2011; Accepted 28 September 2011

Academic Editor: Adhemar Longatto-Filho

Copyright © 2012 E. Guzmán-Olea et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. C. Mougin, V. Dalstein, J. L. Prétet, C. Gay, J. P. Schaal, and D. Riethmuller, “Epidemiology of HPV cervical infections: recent knowledge,” Presse Medicale, vol. 30, no. 20, pp. 1017–1023, 2001. View at Google Scholar · View at Scopus
  2. C. Mougin, L. Mo, and V. Dalstein, “Natural history of papillomavirus infections,” Revue du Praticien, vol. 56, no. 17, pp. 1883–1889, 2006. View at Google Scholar · View at Scopus
  3. B. C. Sheu, W. C. Chang, H. H. Lin, S. N. Chow, and S. C. Huang, “Immune concept of human papillomaviruses and related antigens in local cancer milieu of human cervical neoplasia,” Journal of Obstetrics and Gynaecology Research, vol. 33, no. 2, pp. 103–113, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  4. L. J. Old, “Tumor immunology: the first century,” Current Opinion in Immunology, vol. 4, no. 5, pp. 603–607, 1992. View at Publisher · View at Google Scholar · View at Scopus
  5. S. L. Giannini, W. Al-Saleh, H. Piron et al., “Cytokine expression in squamous intraepithelial lesions of the uterine cervix: implications for the generation of local immunosuppression,” Clinical and Experimental Immunology, vol. 113, no. 2, pp. 183–189, 1998. View at Publisher · View at Google Scholar · View at Scopus
  6. J. M. Alcocer-González, J. Berumen, R. Taméz-Guerra et al., “In vivo expression of immunosuppressive cytokines in human papillomavirus-transfonned cervical cancer cells,” Viral Immunology, vol. 19, no. 3, pp. 481–491, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  7. C. E. Díaz-Benítez, K. R. Navarro-Fuentes, J. A. Flores-Sosa et al., “CD3ζ expression and T cell proliferation are inhibited by TGF-β1 and IL-10 in cervical cancer patients,” Journal of Clinical Immunology, vol. 29, no. 4, pp. 532–544, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  8. T. D. De Gruijl, H. J. Bontkes, F. Peccatori et al., “Expression of CD3-ζ on T-cells in primary cervical carcinoma and in metastasis-positive and -negative pelvic lymph nodes,” British Journal of Cancer, vol. 79, no. 7-8, pp. 1127–1132, 1999. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  9. A. D. Santin, A. Ravaggi, S. Bellone et al., “Tumor-infiltrating lymphocytes contain higher numbers of type 1 cytokine expressors and DR+ T cells compared with lymphocytes from tumor draining lymph nodes and peripheral blood in patients with cancer of the uterine cervix,” Gynecologic Oncology, vol. 81, no. 3, pp. 424–432, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  10. B. C. Sheu, R. H. Lin, H. C. Lien, H. N. Ho, S. M. Hsu, and S. C. Huang, “Predominant Th2/Tc2 polarity of tumor-infiltrating lymphocytes in human cervical cancer,” Journal of Immunology, vol. 167, no. 5, pp. 2972–2978, 2001. View at Google Scholar · View at Scopus
  11. V. H. Bermudez-Morales, L. X. Gutiérrez, J. M. Alcocer-González, A. Burguete, and V. Madrid-Marina, “Correlation between IL-10 gene expression and HPV infection in cervical cancer: a mechanism for immune response escape,” Cancer Investigation, vol. 26, no. 10, pp. 1037–1043, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  12. A. G. Bais, I. Beckmann, J. Lindemans et al., “A shift to a peripheral Th2-type cytokine pattern during the carcinogenesis of cervical cancer becomes manifest in CIN III lesions,” Journal of Clinical Pathology, vol. 58, no. 10, pp. 1096–1100, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  13. T. D. De Gruijl, H. J. Bontkes, A. J. C. Van den Muysenberg et al., “Differences in cytokine mRNA profiles between premalignant and malignant lesions of the uterine cervix,” European Journal of Cancer, vol. 35, no. 3, pp. 490–497, 1999. View at Publisher · View at Google Scholar · View at Scopus
  14. D. F. Fiorentino, A. Zlotnik, T. R. Mosmann, M. Howard, and A. O'Garra, “IL-10 inhibits cytokine production by activated macrophages,” Journal of Immunology, vol. 147, no. 11, pp. 3815–3822, 1991. View at Google Scholar · View at Scopus
  15. S. M. Shondel, C. W. Helm, C. Gercel-Taylor, and D. D. Taylor, “Differential expression of T-cell CD3-zeta chains in patients with cervical dysplasia before and after treatment,” International Journal of Gynecological Cancer, vol. 17, no. 6, pp. 1278–1282, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  16. A. P. Lepique, K. R. P. Daghastanli, I. Cuccovia, and L. L. Villa, “HPV16 tumor associated macrophages suppress antitumor T cell responses,” Clinical Cancer Research, vol. 15, no. 13, pp. 4391–4400, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  17. A. Bolpetti, J. S. Silva, L. L. Villa, and A. P. Lepique, “Interleukin-10 production by tumor infiltrating macrophages plays a role in Human Papillomavirus 16 tumor growth,” BMC Immunology, vol. 11, article 27, 2010. View at Publisher · View at Google Scholar · View at PubMed
  18. D. I. Gabrilovich, M. P. Velders, E. M. Sotomayor, and W. M. Kast, “Mechanism of immune dysfunction in cancer mediated by immature Gr-1+ myeloid cells,” Journal of Immunology, vol. 166, no. 9, pp. 5398–5406, 2001. View at Google Scholar · View at Scopus
  19. H. Trottier and E. L. Franco, “Human papillomavirus and cervical cancer: burden of illness and basis for prevention,” American Journal of Managed Care, vol. 12, no. 17, pp. S462–S472, 2006. View at Google Scholar · View at Scopus
  20. M. Stanley, “Immune responses to human papillomavirus,” Vaccine, vol. 24, no. 1, pp. S16–S22, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  21. O. Peralta-Zaragoza, V. Bermúdez-Morales, L. Gutiérrez-Xicotencatl, J. Alcocer-González, F. Recillas-Targa, and V. Madrid-Marina, “E6 and E7 oncoproteins from human papillomavirus type 16 induce activation of human transforming growth factor β1 promoter throughout Sp1 recognition sequence,” Viral Immunology, vol. 19, no. 3, pp. 468–480, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  22. V. H. Bermúdez-Morales, O. Peralta-Zaragoza, J. M. Alcocer-González, J. Moreno, and V. Madrid-Marina, “IL-10 expression is regulated by HPV E2 protein in cervical cancer cells,” Molecular Medicine Reports, vol. 4, no. 2, pp. 369–375, 2011. View at Publisher · View at Google Scholar · View at PubMed
  23. M. Ahmad, R. C. Rees, and S. A. Ali, “Escape from immunotherapy: possible mechanisms that influence tumor regression/progression,” Cancer Immunology, Immunotherapy, vol. 53, no. 10, pp. 844–854, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  24. M. C. Lai, B. H. Teh, and W. Y. Tarn, “A human papillomavirus E2 transcriptional activator: the interactions with cellular splicing factors and potential function in pre-mRNA processing,” The Journal of Biological Chemistry, vol. 274, no. 17, pp. 11832–11841, 1999. View at Publisher · View at Google Scholar · View at Scopus
  25. C. C. Baker, W. C. Phelps, V. Lindgren, M. J. Braun, M. A. Gonda, and P. M. Howley, “Structural and transcriptional analysis of human papilloma- virus type 16 sequences in cervical carcinoma cell lines,” Journal of Virology, vol. 19, pp. 962–971, 1987. View at Google Scholar
  26. F. Thierry and M. Yaniv, “The BPV1-E2 trans-acting protein can be either an activator or a repressor of the HPV18 regulatory region,” The EMBO Journal, vol. 6, no. 11, pp. 3391–3397, 1987. View at Google Scholar · View at Scopus
  27. E. S. Hwang, L. K. Naegerm, and D. DiMario, “Acti- vation of the endogenous p53 growth in- hibitory pathway in HeLa cervical carci- noma cells by expression of the bovine papillomavirus E2 gene,” Oncogene, vol. 12, pp. 795–803, 1996. View at Google Scholar
  28. E. S. Hwang, D. J. Riese, J. Settleman et al., “Inhibition of cervical carcinoma cell line proliferation by the introduction of a bovine papillomavirus regulatory gene,” Journal of Virology, vol. 67, no. 7, pp. 3720–3729, 1993. View at Google Scholar · View at Scopus
  29. C. Desaintes, C. Demeret, S. Goyat, M. Yaniv, and F. Thierry, “Expression of the papillomavirus E2 protein in HeLa cells leads to apoptosis,” The EMBO Journal, vol. 16, no. 3, pp. 504–514, 1997. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  30. J. J. Dowhanick, A. A. McBride, and P. M. Howley, “Suppression of cellular proliferation by the papillomavirus E2 protein,” Journal of Virology, vol. 69, no. 12, pp. 7791–7799, 1995. View at Google Scholar · View at Scopus
  31. C. Demeret, A. Garcia-Carranca, and F. Thierry, “Transcription-independent triggering of the extrinsic pathway of apoptosis by human papillomavirus 18 E2 protein,” Oncogene, vol. 22, no. 2, pp. 168–175, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  32. S. Blachon and C. Demeret, “The regulatory E2 proteins of human genital papillomaviruses are pro-apoptotic,” Biochimie, vol. 85, no. 8, pp. 813–819, 2003. View at Publisher · View at Google Scholar · View at Scopus
  33. C. Desaintes, S. Goyat, S. Garbay, M. Yaniv, and F. Thierry, “Papillomavirus E2 induces p53-independent apoptosis in HeLa cells,” Oncogene, vol. 18, no. 32, pp. 4538–4545, 1999. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  34. K. Webster, J. Parish, M. Pandya, P. L. Stern, A. R. Clarke, and K. Gaston, “The human papillomavirus (HPV) 16 E2 protein induces apoptosis in the absence of other HPV proteins and via a p53-dependent pathway,” The Journal of Biological Chemistry, vol. 275, no. 1, pp. 87–94, 2000. View at Publisher · View at Google Scholar · View at Scopus
  35. C. Rosales, V. Valadez Graham, G. A. Rosas, H. Merchant, and R. Rosales, “A recombinant vaccinia virus containing the papilloma E2 protein promotes tumor regression by stimulating macrophage antibody-dependent cytotoxicity,” Cancer Immunology Immunotherapy, vol. 49, no. 7, pp. 347–360, 2000. View at Google Scholar · View at Scopus
  36. V. V. Graham, G. Sutter, M. V. José et al., “Human tumor growth is inhibited by a vaccinia virus carrying the E2 gene of bovine papillomavirus,” Cancer, vol. 88, no. 7, pp. 1650–1662, 2000. View at Publisher · View at Google Scholar · View at Scopus
  37. J. Berumen, L. Casas, E. Segura, J. L. Amezcua, and A. Garcia-Carranca, “Genome amplification of human papillomavirus types 16 and 18 in cervical carcinomas is related to the retention of E1/E2 genes,” International Journal of Cancer, vol. 56, no. 5, pp. 640–645, 1994. View at Google Scholar · View at Scopus
  38. V. H. Bermúdez-Morales, O. Peralta-Zaragoza, E. Guzmán-Olea et al., “HPV 16 E2 protein induces apoptosis in human and murine HPV 16 transformed epithelial cells and has antitumoral effects in vivo,” Tumor Biology, vol. 30, no. 2, pp. 61–72, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  39. G. Dranoff, “Cytokines in cancer pathogenesis and cancer therapy,” Nature Reviews Cancer, vol. 4, no. 1, pp. 11–22, 2004. View at Google Scholar · View at Scopus
  40. M. Clerici, M. Merola, E. Ferrario et al., “Cytokine production patterns in cervical intraepithelial neoplasia: association with human papillomavirus infection,” Journal of the National Cancer Institute, vol. 89, no. 3, pp. 245–250, 1997. View at Google Scholar · View at Scopus
  41. V. H. Bermúdez-Morales, O. Peralta-Zaragoza, and V. Madrid-Marina, “Gene therapy with cytokines against cervical cancer,” Salud Publica de Mexico, vol. 47, no. 6, pp. 458–468, 2005. View at Google Scholar
  42. M. Del Vecchio, E. Bajetta, S. Canova et al., “Interleukin-12: biological properties and clinical application,” Clinical Cancer Research, vol. 13, no. 16, pp. 4677–4685, 2007. View at Publisher · View at Google Scholar · View at PubMed
  43. X. Yin, X. Yan, Q. Yang, H. Cao, and H. Liang, “AntiTumor mechanism of recombinant murine interleukin-12 vaccine,” Cancer Biotherapy and Radiopharmaceuticals, vol. 25, no. 3, pp. 263–268, 2010. View at Publisher · View at Google Scholar · View at PubMed
  44. C. E. Steding, S.-T. Wu, Y. Zhang, M.-H. Jeng, B. D. Elzey, and C. Kao, “The role of interleukin-12 on modulating myeloid-derived suppressor cells, increasing overall survival and reducing metastasis,” Immunology, vol. 133, no. 2, pp. 221–238, 2011. View at Publisher · View at Google Scholar · View at PubMed
  45. L. H. L. Marchi, T. Paschoalin, L. R. Travassos, and E. G. Rodrigues, “Gene therapy with interleukin-10 receptor and interleukin-12 induces a protective interferon-γ-dependent response against B16F10-Nex2 melanoma,” Cancer Gene Therapy, vol. 18, no. 2, pp. 110–122, 2010. View at Publisher · View at Google Scholar · View at PubMed
  46. H. Komita, X. Zhao, A. K. Katakam et al., “Conditional interleukin-12 gene therapy promotes safe and effective antitumor immunity,” Cancer Gene Therapy, vol. 16, no. 12, pp. 883–891, 2009. View at Publisher · View at Google Scholar · View at PubMed
  47. W. S. Ahn, S. M. Bae, T. Y. Kim et al., “A therapy modality using recombinant IL-12 adenovirus plus E7 protein in a human papillomavirus 16 E6/E7-associated cervical cancer animal model,” Human Gene Therapy, vol. 14, no. 15, pp. 1389–1399, 2003. View at Publisher · View at Google Scholar · View at PubMed
  48. Y. K. He, V. W. Y. Lui, J. Baar et al., “Potentiation of E7 antisense RNA-induced antitumor immunity by co-delivery of IL-12 gene in HPV16 DNA-positive mouse tumor,” Gene Therapy, vol. 5, no. 11, pp. 1462–1471, 1998. View at Google Scholar
  49. S. Hallez, O. Detremmerie, C. Giannouli et al., “Interleukin-12-secreting human papillomavirus type 16-transformed cells provide a potent cancer vaccine that generates E7-directed immunity,” International Journal of Cancer, vol. 81, no. 3, pp. 428–437, 1999. View at Google Scholar
  50. K. Taga, H. Mostowski, and G. Tosato, “Human interleukin-10 can directly inhibit T-cell growth,” Blood, vol. 81, no. 11, pp. 2964–2971, 1993. View at Google Scholar
  51. M. Indrová, J. Bubeník, R. Mikysková et al., “Chemoimmunotherapy in mice carrying HPV16-associated, MHC class I+ and class I- tumours: effects of CBM-4A potentiated with IL-2, IL-12, GM-CSF and genetically modified tumour vaccines,” International Journal of Oncology, vol. 22, no. 3, pp. 691–695, 2003. View at Google Scholar
  52. F. De vita, M. Orditura, and G. Galizia, “Serum interleukin-10 is an independent prognos-tic factor in advanced solid tumors,” Oncology Reports, vol. 7, pp. 357–361, 2000. View at Google Scholar
  53. S. Mocellin, F. M. Marincola, and H. A. Young, “Interleukin-10 and the immune response against cancer: a counterpoint,” Journal of Leukocyte Biology, vol. 78, no. 5, pp. 1043–1051, 2005. View at Publisher · View at Google Scholar · View at PubMed
  54. D. F. Fiorentino, A. Zlotnik, P. Vieira et al., “IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells,” Journal of Immunology, vol. 146, no. 10, pp. 3444–3451, 1991. View at Google Scholar
  55. R. De Waal Malefyt, J. Haanen, H. Spits et al., “Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression,” Journal of Experimental Medicine, vol. 174, no. 4, pp. 915–924, 1991. View at Google Scholar
  56. I. A. MacNeil, T. Suda, K. W. Moore, T. R. Mosmann, and A. Zlotnik, “IL-10, a novel growth cofactor for mature and immature T cells,” Journal of Immunology, vol. 145, no. 12, pp. 4167–4173, 1990. View at Google Scholar
  57. W. F. Chen and A. Zlotnik, “IL-10: a novel cytotoxic T cell differentiation factor,” Journal of Immunology, vol. 147, no. 2, pp. 528–534, 1991. View at Google Scholar
  58. N. F. Go, B. E. Castle, R. Barrett et al., “Interleukin 10, a novel B cell stimulatory factor: unresponsiveness of X chromosome-linked immunodeficiency B cells,” Journal of Experimental Medicine, vol. 172, no. 6, pp. 1625–1631, 1990. View at Publisher · View at Google Scholar
  59. J. Kim, R. L. Modlin, R. L. Moy et al., “IL-10 production in cutaneous basal and squamous cell carcinomas: a mechanism for evading the local T cell immune response,” Journal of Immunology, vol. 155, no. 4, pp. 2240–2247, 1995. View at Google Scholar
  60. F. Y. Yue, R. Dummer, R. Geertsen et al., “Interleukin-10 is a growth factor for human melanoma cells and down-regulates HLA class-I, HLA class-II and ICAM-1 molecules,” International Journal of Cancer, vol. 71, no. 4, pp. 630–637, 1997. View at Publisher · View at Google Scholar
  61. M. L. García-Hernández, R. Hernández-Pando, P. Gariglio, and J. Berumen, “Interleukin-10 promotes B16-melanoma growth by inhibition of macrophage functions and induction of tumour and vascular cell proliferation,” Immunology, vol. 105, no. 2, pp. 231–243, 2002. View at Publisher · View at Google Scholar
  62. P. Matar, V. R. Rozados, S. I. Gervasoni, and O. G. Scharovsky, “Down regulation of T-cell-derived IL-10 production by low-dose cyclophosphamide treatment in tumor-bearing rats restores in vitro normal lymphoproliferative response,” International Immunopharmacology, vol. 1, no. 2, pp. 307–319, 2001. View at Publisher · View at Google Scholar
  63. V. M. Jovasevic, L. Gorelik, J. A. Bluestone, and M. B. Mokyr, “Importance of IL-10 for CTLA-4-Mediated Inhibition of Tumor-Eradicating Immunity,” Journal of Immunology, vol. 172, no. 3, pp. 1449–1454, 2004. View at Google Scholar
  64. A. P. Vicari, C. Chiodoni, C. Vaure et al., “Reversal of tumor-induced dendritic cell paralysis by CpG immunostimulatory oligonucleotide and anti-interleukin 10 receptor antibody,” Journal of Experimental Medicine, vol. 196, no. 4, pp. 541–549, 2002. View at Publisher · View at Google Scholar
  65. B. G. Kim, H. G. Joo, I. S. Chung, H. Y. Chung, H. J. Woo, and Y. S. Yun, “Inhibition of interleukin-10 (IL-10) production from MOPC 315 tumor cells by IL-10 antisense oligodeoxynucleotides enhances cell-mediated immune responses,” Cancer Immunology Immunotherapy, vol. 49, no. 8, pp. 433–440, 2000. View at Google Scholar
  66. M. Lagos-Quintana, R. Rauhut, W. Lendeckel, and T. Tuschl, “Identification of novel genes coding for small expressed RNAs,” Science, vol. 294, no. 5543, pp. 853–858, 2001. View at Publisher · View at Google Scholar · View at PubMed
  67. N. C. Lau, L. P. Lim, E. G. Weinstein, and D. P. Bartel, “An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans,” Science, vol. 294, no. 5543, pp. 858–862, 2001. View at Publisher · View at Google Scholar · View at PubMed
  68. R. C. Lee and V. Ambros, “An extensive class of small RNAs in Caenorhabditis elegans,” Science, vol. 294, no. 5543, pp. 862–864, 2001. View at Publisher · View at Google Scholar · View at PubMed
  69. J. G. Doench, C. P. Petersen, and P. A. Sharp, “siRNAs can function as miRNAs,” Genes and Development, vol. 17, no. 4, pp. 438–442, 2003. View at Publisher · View at Google Scholar · View at PubMed
  70. S. M. Elbashir, J. Harborth, W. Lendeckel, A. Yalcin, K. Weber, and T. Tuschl, “Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells,” Nature, vol. 411, no. 6836, pp. 494–498, 2001. View at Publisher · View at Google Scholar · View at PubMed
  71. S. M. Elbashir, J. Martinez, A. Patkaniowska, W. Lendeckel, and T. Tuschl, “Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate,” The EMBO Journal, vol. 20, no. 23, pp. 6877–6888, 2001. View at Publisher · View at Google Scholar · View at PubMed
  72. M. Jiang and J. Milner, “Selective silencing of viral gene expression in HPV-positive human cervical carcinoma cells treated with siRNA, a primer of RNA interference,” Oncogene, vol. 21, no. 39, pp. 6041–6048, 2002. View at Publisher · View at Google Scholar · View at PubMed
  73. M. Yoshinouchi, T. Yamada, M. Kizaki et al., “In vitro and in vivo growth suppression of human papillomavirus 16-positive cervical cancer cells by E6 siRNA,” Molecular Therapy, vol. 8, no. 5, pp. 762–768, 2003. View at Publisher · View at Google Scholar
  74. K. Butz, T. Ristriani, A. Hengstermann, C. Denk, M. Scheffner, and F. Hoppe-Seyler, “siRNA targeting of the viral E6 oncogene efficiently kills human papillomavirus-positive cancer cells,” Oncogene, vol. 22, no. 38, pp. 5938–5945, 2003. View at Publisher · View at Google Scholar · View at PubMed
  75. J. S. Lea, N. Sunaga, M. Sato et al., “Silencing of HPV 18 oncoproteins with RNA interference causes growth inhibition of cervical cancer cells,” Reproductive Sciences, vol. 14, no. 1, pp. 20–28, 2007. View at Publisher · View at Google Scholar · View at PubMed
  76. K. Butz, C. Denk, A. Ullmann, M. Scheffner, and F. Hoppe-Seyler, “Induction of apoptosis in human papillomavirus-positive cancer cells by peptide aptamers targeting the viral E6 oncoprotein,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 12, pp. 6693–6697, 2000. View at Publisher · View at Google Scholar · View at PubMed
  77. M. Scheffner, B. A. Werness, J. M. Huibregtse, A. J. Levine, and P. M. Howley, “The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53,” Cell, vol. 63, no. 6, pp. 1129–1136, 1990. View at Publisher · View at Google Scholar
  78. M. Thomas and L. Banks, “Inhibition of Bak-induced apoptosis by HPV-18 E6,” Oncogene, vol. 17, no. 23, pp. 2943–2954, 1998. View at Google Scholar
  79. M. Filippova, L. Parkhurst, and P. J. Duerksen-Hughes, “The human papillomavirus 16 E6 protein binds to Fas-associated death domain and protects cells from Fas-triggered apoptosis,” The Journal of Biological Chemistry, vol. 279, no. 24, pp. 25729–25744, 2004. View at Publisher · View at Google Scholar · View at PubMed
  80. T. O. Garnett, M. Filippova, and P. J. Duerksen-Hughes, “Accelerated degradation of FADD and procaspase 8 in cells expressing human papilloma virus 16 E6 impairs TRAIL-mediated apoptosis,” Cell Death and Differentiation, vol. 13, no. 11, pp. 1915–1926, 2006. View at Publisher · View at Google Scholar · View at PubMed
  81. S. Gross-Mesilaty, E. Reinstein, B. Bercovich et al., “Basal and human papillomavirus E6 oncoprotein-induced degradation of Myc proteins by the ubiquitin pathway,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 14, pp. 8058–8063, 1998. View at Publisher · View at Google Scholar
  82. A. Lagunas-Martínez, V. Madrid-Marina, and P. Gariglio, “Modulation of apoptosis by early human papillomavirus proteins in cervical cancer,” Biochimica et Biophysica Acta, vol. 1805, no. 1, pp. 6–16, 2010. View at Publisher · View at Google Scholar · View at PubMed
  83. M. Filippova, H. Song, J. L. Connolly, T. S. Dermody, and P. J. Duerksen-Hughes, “The human papillomavirus 16 E6 protein binds to tumor necrosis factor (TNF) R1 and protects cells from TNF-induced apoptosis,” The Journal of Biological Chemistry, vol. 277, no. 24, pp. 21730–21739, 2002. View at Publisher · View at Google Scholar · View at PubMed
  84. X. Luo, I. Budihardjo, H. Zou, C. Slaughter, and X. Wang, “Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors,” Cell, vol. 94, no. 4, pp. 481–490, 1998. View at Google Scholar
  85. H. Kuwano, K. Sumiyoshi, K. Sonoda et al., “Pathogenesis of esophageal squamous cell carcinoma with lymphoid stroma,” Hepato-Gastroenterology, vol. 48, no. 38, pp. 458–461, 2001. View at Google Scholar
  86. L. N. Putral, M. J. Bywater, W. Gu et al., “RNA interference against human papillomavirus oncogenes in cervical cancer cells results in increased sensitivity to cisplatin,” Molecular Pharmacology, vol. 68, no. 5, pp. 1311–1319, 2005. View at Publisher · View at Google Scholar · View at PubMed
  87. X. Y. Niu, Z. L. Peng, W. Q. Duan, H. Wang, and P. Wang, “Inhibition of HPV 16 E6 oncogene expression by RNA interference in vitro and in vivo,” International Journal of Gynecological Cancer, vol. 16, no. 2, pp. 743–751, 2006. View at Publisher · View at Google Scholar · View at PubMed
  88. M. Jiang, C. P. Rubbi, and J. Milner, “Gel-based application of siRNA to human epithelial cancer cells induces RNAi-dependent apoptosis,” Oligonucleotides, vol. 14, no. 4, pp. 239–248, 2004. View at Google Scholar
  89. F. Takuma, S. Miyuki, I. Eri et al., “Intratumor injection of small interfering RNA-targeting human papillomavirus 18 E6 and E7 successfully inhibits the growth of cervical cancer,” International Journal of Oncology, vol. 29, no. 3, pp. 541–548, 2006. View at Google Scholar
  90. W. Gu, L. Putral, and N. McMillan, “SiRNA and shRNA as anticancer agents in a cervical cancer model,” Methods in Molecular Biology, vol. 442, pp. 159–172, 2008. View at Publisher · View at Google Scholar · View at PubMed
  91. R. Kuner, M. Vogt, H. Sultmann et al., “Identification of cellular targets for the human papillomavirus E6 and E7 oncogenes by RNA interference and transcriptome analyses,” Journal of Molecular Medicine, vol. 85, no. 11, pp. 1253–1262, 2007. View at Publisher · View at Google Scholar · View at PubMed
  92. M. Peter, C. Rosty, J. Couturier, F. Radvanyi, H. Teshima, and X. Sastre-Garau, “MYC activation associated with the integration of HPV DNA at the MYC locus in genital tumors,” Oncogene, vol. 25, no. 44, pp. 5985–5993, 2006. View at Publisher · View at Google Scholar · View at PubMed
  93. R. A. DeFilippis, E. C. Goodwin, L. Wu, and D. DiMaio, “Endogenous human papillomavirus E6 and E7 proteins differentially regulate proliferation, senescence, and apoptosis in HeLa cervical carcinoma cells,” Journal of Virology, vol. 77, no. 2, pp. 1551–1563, 2003. View at Publisher · View at Google Scholar
  94. R. Koivusalo, E. Krausz, H. Helenius, and S. Hietanen, “Chemotherapy compounds in cervical cancer cells primed by reconstitution of p53 function after short interfering RNA-mediated degradation of human papillomavirus 18 E6 mRNA: opposite effect of siRNA in combination with different drugs,” Molecular Pharmacology, vol. 68, no. 2, pp. 372–382, 2005. View at Publisher · View at Google Scholar · View at PubMed
  95. K. Yamato, T. Yamada, M. Kizaki et al., “New highly potent and specific E6 and E7 siRNAs for treatment of HPV16 positive cervical cancer,” Cancer Gene Therapy, vol. 15, pp. 140–153, 2008. View at Google Scholar
  96. N. Sima, W. Wang, D. Kong et al., “RNA interference against HPV16 E7 oncogene leads to viral E6 and E7 suppression in cervical cancer cells and apoptosis via upregulation of Rb and p53,” Apoptosi, vol. 13, pp. 273–281, 2008. View at Google Scholar
  97. J. Salazar-León, F. Reyes-Román, A. Meneses-Acosta et al., “Silencing of HPV16 E6 and E7 oncogenic activities by small interference RNA induces autophagy and apoptosis in human cervical cancer cells,” Journal of Nucleic Acids Investigation, vol. 2, pp. 59–69, 2011. View at Google Scholar