Human papillomavirus and molecular considerations for cancer risk

Cancer

Volumn 113, Issue 10 SUPPL., 2008, Pages 2981-2994

  Whiteside, Martin A ^a   Siegel, Erin M ^b   Unger, Elizabeth R ^c  

^a TENNESSEE DEPARTMENT OF HEALTH   (United States)

^b H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

^c CENTERS FOR DISEASE CONTROL AND PREVENTION   (United States)

Author keywords

Apoptosis; Biologic markers; Cell adhesion; Cell cycle; DNA methylation; DNA repair; E6 protein; E7 protein; Human papillomavirus

Indexed keywords

BIOLOGICAL MARKER; MOLECULAR MARKER; PROTEIN E6; PROTEIN E7; PROTEIN P53; RETINOBLASTOMA PROTEIN; VIRUS DNA;

APOPTOSIS; CANCER GRADING; CANCER GROWTH; CANCER INVASION; CANCER RISK; CANCER SCREENING; CELL ADHESION; CELL CYCLE REGULATION; DNA METHYLATION; DNA REPAIR; DNA REPLICATION; DYSPLASIA; IMMUNE RESPONSE; NONHUMAN; PAPANICOLAOU TEST; PAPILLOMA VIRUS; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; REVIEW; VIRUS CARCINOGENESIS; VIRUS CELL INTERACTION;

ALPHAPAPILLOMAVIRUS; DNA METHYLATION; FEMALE; HUMANS; ONCOGENE PROTEINS, VIRAL; PAPILLOMAVIRUS INFECTIONS; REPRESSOR PROTEINS; RISK; TUMOR MARKERS, BIOLOGICAL; UTERINE CERVICAL NEOPLASMS; VIRAL PROTEINS;

EID: 56449129788     PISSN: 0008543X     EISSN: 10970142     Source Type: Journal    
DOI: 10.1002/cncr.23750     Document Type: Review

References (171)

1. Chen Z, Schiffman M, Herrero R, Desalle R, Burk RD. Human papillomavirus (HPV) types 101 and 103 isolated from cervicovaginal cells lack an E6 open reading frame (ORF) and are related to gamma-papillomaviruses. Virology. 2007;360:447-453.
2. Janicek MF, Averette HE. Cervical cancer: prevention, diagnosis, and therapeutics. CA Cancer J Clin. 2001;51:92-114.
3. Stubenrauch F, Laimins LA. Human papillomavirus life cycle: active and latent phases. Semin Cancer Biol. 1999;9:379-386.
4. zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer. 2002;2:342-350.
5. Middleton K, Peh W, Southern S, et al. Organization of human papillomavirus productive cycle during neoplastic progression provides a basis for selection of diagnostic markers. J Virol. 2003;77:10186-10201.
6. Wang SS, Hildesheim A. Chapter 5: viral and host factors in human papillomavirus persistence and progression. J Natl Cancer Inst Monogr. 2003:35-40.
7. Badaracco G, Venuti A, Sedati A, Marcante ML. HPV16 and HPV18 in genital tumors: significantly different levels of viral integration and correlation to tumor invasiveness. J Med Virol. 2002;67:574-582.
8. Heselmeyer K, Schrock E, du Manoir S, et al. Gain of chromosome 3q defines the transition from severe dysplasia to invasive carcinoma of the uterine cervix. Proc Natl Acad Sci U S A. 1996;93:479-484.
9. Doerfler W. Abortive infection and malignant transformation by adenoviruses: integration of viral DNA and control of viral gene expression by specific patterns of DNA methylation. Adv Virus Res. 1991;39:89-128.
10. Badal V, Chuang LS, Tan EH, et al. CpG methylation of human papillomavirus type 16 DNA in cervical cancer cell lines and in clinical specimens: genomic hypomethylation correlates with carcinogenic progression. J Virol. 2003;77:6227-6234.
11. Turan T, Kalantari M, Calleja-Macias IE, et al. Methylation of the human papillomavirus-18 L1 gene: a biomarker of neoplastic progression? Virology. 2006;349:175-183.
12. Kalantari M, Calleja-Macias IE, Tewari D, et al. Conserved methylation patterns of human papillomavirus type 16 DNA in asymptomatic infection and cervical neoplasia. J Virol. 2004;78:12762-12772.
13. Badal S, Badal V, Calleja-Macias IE, et al. The human papillomavirus-18 genome is efficiently targeted by cellular DNA methylation. Virology. 2004;324:483-492.
14. Avvakumov N, Torchia J, Mymryk JS. Interaction of the HPV E7 proteins with the pCAF acetyltransferase. Oncogene. 2003;22:3833-3841.
15. Burgers WA, Blanchon L, Pradhan S, de Launoit Y, Kouzarides T, Fuks F. Viral oncoproteins target the DNA methyltransferases. Oncogene. 2007;26:1650-1655.
16. Tungteakkhun SS, Duerksen-Hughes PJ. Cellular binding partners of the human papillomavirus E6 protein. Arch Virol. 2008;153:397-408.
17. Munger K, Basile JR, Duensing S, et al. Biological activities and molecular targets of the human papillomavirus E7 oncoprotein. Oncogene. 2001;20:7888-7898.
18. McMurray HR, McCance DJ. Degradation of p53, not telomerase activation, by E6 is required for bypass of crisis and immortalization by human papillomavirus type 16 E6/E7. J Virol. 2004;78:5698-5706.
19. Li H, Xu D, Li J, Berndt MC, Liu JP. Transforming growth factor beta suppresses human telomerase reverse transcriptase (hTERT) by Smad3 interactions with c-Myc and the hTERT gene. J Biol Chem. 2006;281:25588-25600.
20. Katzenellenbogen RA, Egelkrout EM, Vliet-Gregg P, Gewin LC, Gafken PR, Galloway DA. NFX1-123 and poly(A) binding proteins synergistically augment activation of telomerase in human papillomavirus type 16 E6-expressing cells. J Virol. 2007;81:3786-3796.
21. Bellon M, Nicot C. Regulation of telomerase and telomeres: human tumor viruses take control. J Natl Cancer Inst. 2008;100:98-108.
22. Oikonomou P, Messinis I, Tsezou A. DNA methylation is not likely to be responsible for hTERT expression in premalignant cervical lesions. Exp Biol Med (Maywood). 2007;232:881-886.
23. Bialik S, Kimchi A. The death-associated protein kinases: structure, function, and beyond. Annu Rev Biochem. 2006;75:189-210.
24. Maiuri MC, Zalckvar E, Kimchi A, Kroemer G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol. 2007;8:741-752.
25. Takizawa S, Nagasaka K, Nakagawa S, et al. Human scribble, a novel tumor suppressor identified as a target of high-risk HPV E6 for ubiquitin-mediated degradation, interacts with adenomatous polyposis coli. Genes Cells. 2006;11:453-464.
26. Ishidate T, Matsumine A, Toyoshima K, Akiyama T. The APC-hDLG complex negatively regulates cell cycle progression from the G0/G1 to S phase. Oncogene. 2000;19:365-372.
27. Ranganathan R, Ross EM. PDZ domain proteins: scaffolds for signaling complexes. Curr Biol. 1997;7:R770-773.
28. Lee C, Laimins LA. Role of the PDZ domain-binding motif of the oncoprotein E6 in the pathogenesis of human papillomavirus type 31. J Virol. 2004;78:12366-12377.
29. Willert K, Jones KA. Wnt signaling: is the party in the nucleus? Genes Dev. 2006;20:1394-1404.
30. Ciruna B, Rossant J. FGF signaling regulates mesoderm cell fate specification and morphogenetic movement at the primitive streak. Dev Cell. 2001;1:37-49.
31. Hubert P, Caberg JH, Gilles C, et al. E-cadherin-dependent adhesion of dendritic and Langerhans cells to keratinocytes is defective in cervical human papillomavirus-associated (pre)neoplastic lesions. J Pathol. 2005;206:346-355.
32. Wilding J, Vousden KH, Soutter WP, McCrea PD, Del Buono R, Pignatelli M. E-cadherin transfection down-regulates the epidermal growth factor receptor and reverses the invasive phenotype of human papilloma virus-transfected keratinocytes. Cancer Res. 1996;56:5285-5292.
33. Perez-Plasencia C, Vazquez-Ortiz G, Lopez-Romero R, Pina-Sanchez P, Moreno J, Salcedo M. Genome wide expression analysis in HPV16 Cervical Cancer: identification of altered metabolic pathways. Infect Agent Cancer. 2007;2:16.
34. Uren A, Fallen S, Yuan H, et al. Activation of the canonical Wnt pathway during genital keratinocyte transformation: a model for cervical cancer progression. Cancer Res. 2005;65:6199-6206.
35. Bayani J, Selvarajah S, Maire G, et al. Genomic mechanisms and measurement of structural and numerical instability in cancer cells. Semin Cancer Biol. 2007;17:5-18.
36. Iftner T, Elbel M, Schopp B, et al. Interference of papillomavirus E6 protein with single-strand break repair by interaction with XRCC1. EMBO J. 2002;21:4741-4748.
37. Zhang Y, Fan S, Meng Q, et al. BRCA1 interaction with human papillomavirus oncoproteins. J Biol Chem. 2005;280:33165-33177.
38. Yarden RI, Papa MZ. BRCA1 at the crossroad of multiple cellular pathways: approaches for therapeutic interventions. Mol Cancer Ther. 2006;5:1396-1404.
39. Xiong J, Fan S, Meng Q, et al. BRCA1 inhibition of telomerase activity in cultured cells. Mol Cell Biol. 2003;23:8668-8690.
40. Ouchi T, Monteiro AN, August A, Aaronson SA, Hanafusa H. BRCA1 regulates p53-dependent gene expression. Proc Natl Acad Sci U S A. 1998;95:2302-2306.
41. Aprelikova ON, Fang BS, Meissner EG, et al. BRCA1-associated growth arrest is RB-dependent. Proc Natl Acad Sci U S A. 1999;96:11866-11871.
42. The ASCUS-LSIL Triage Study (ALTS) Group. Results of a randomized trial on the management of cytology interpretations of atypical squamous cells of undetermined significance. Am J Obstet Gynecol. 2003;188:1383-1392.
43. Bulkmans NWJ, Berkhof J, Rozendaal L, et al. Human papillomavirus DNA testing for the detection of cervical intraepithelial neoplasia grade 3 and cancer: 5-year follow-up of a randomized controlled implementation trial. Lancet. 2007;370:1764-1772.
44. Mayrand M-H, Duarte-Franco E, Rodrigues I, et al. Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer. N Engl J Med. 2007;357:1579-1588.
45. Naucler P, Ryd W, Tornberg S, et al. Human papillomavirus and Papanicolaou tests to screen for cervical cancer. N Engl J Med. 2007;357:1589-1597.
46. Peyton CL, Gravitt PE, Hunt WC, et al. Determinants of genital human papillomavirus detection in a US population. J Infect Dis. 2001;183:1554-1564.
47. Martin CM, Kehoe L, Spillane CO, O'Leary JJ. Gene discovery in cervical cancer. Towards diagnostic and therapeutic biomarkers. Mol Diag Ther. 2007;11:277-290.
48. Malinowski DP. Multiple biomarkers in molecular oncology. I. Molecular diagnostics applications in cervical cancer detection. Expert Rev Mol Diagn. 2007;7:117-131.
49. Unger ER, Steinau M, Rajeevan MS, Swan D, Lee DR, Vernon SD. Molecular markers for early detection of cervical neoplasia. Dis Markers. 2004;20:103-116.
50. Liu H, Shi J, Wilkerson M, et al. Immunohistochemical detection of p16INK4a in liquid-based cytology specimens on cell block sections. Cancer. 2007;111:74-82.
51. Eleuterio J Jr, Giraldo PC, Goncalves AK, et al. Prognostic markers of high-grade squamous intraepithelial lesions: the role of p16INK4a and high-risk human papillomavirus. Acta Obstet Gynecol Scand. 2007;86:94-98.
52. Meyer JL, Hanlon DW, Andersen BT, Rasmussen OF, Bisgaard K. Evaluation of p16INK4a expression in ThinPrep cervical specimens with the CINtec p16INK4a assay: correlation with biopsy follow-up results. Cancer. 2007;111:83-92.
53. Wentzensen N, von Knebel Doeberitz M. Biomarkers in cervical cancer screening. Dis Markers. 2007;23:315-330.
54. Mukherjee G, Muralidhar B, Bafna UD, Laskey RA, Coleman N. MCM immunocytochemistry as a first line cervical screening test in developing countries: a prospective cohort study in a regional cancer centre in India. Br J Cancer. 2007;96:1107-1111.
55. Williams GH, Romanowski P, Morris L, et al. Improved cervical smear assessment using antibodies against proteins that regulate DNA replication. Proc Natl Acad Sci USA. 1998;95:14932-14937.
56. Doorbar J, Cubie H. Molecular basis for advances in cervical screening. Mol Diagn. 2005;9:129-142.
57. Wisman GB, Nijhuis ER, Hoque MO, et al. Assessment of gene promoter hypermethylation for detection of cervical neoplasia. Int J Cancer. 2006;119:1908-1914.
58. Handa K, Yugawa T, Narisawa-Saito M, Ohno S, Fujita M, Kiyono T. E6AP-dependent degradation of DLG4/PSD95 by high-risk human papillomavirus type 18 E6 protein. J Virol. 2007;81:1379-1389.
59. Kiyono T, Hiraiwa A, Fujita M, Hayashi Y, Akiyama T, Ishibashi M. Binding of high-risk human papillomavirus E6 oncoproteins to the human homologue of the Drosophila discs large tumor suppressor protein. Proc Natl Acad Sci U S A. 1997;94:11612-11616.
60. Nakagawa S, Huibregtse JM. Human scribble (Vartul) is targeted for ubiquitin-mediated degradation by the highrisk papillomavirus E6 proteins and the E6AP ubiquitin-protein ligase. Mol Cell Biol. 2000;20:8244-8253.
61. Storrs CH, Silverstein SJ. PATJ, a tight junction-associated PDZ protein, is a novel degradation target of high-risk human papillomavirus E6 and the alternatively spliced isoform 18 E6. J Virol. 2007;81:4080-4090.
62. Tong X, Howley PM. The bovine papillomavirus E6 oncoprotein interacts with paxillin and disrupts the actin cytoskeleton. Proc Natl Acad Sci U S A. 1997;94:4412-4417.
63. Degenhardt YY, Silverstein S. Interaction of zyxin, a focal adhesion protein, with the e6 protein from human papillomavirus type 6 results in its nuclear translocation. J Virol. 2001;75:11791-11802.
64. Glaunsinger BA, Lee SS, Thomas M, Banks L, Javier R. Interactions of the PDZ-protein MAGI-1 with adenovirus E4-ORF1 and high-risk papillomavirus E6 oncoproteins. Oncogene. 2000;19:5270-5280.
65. Thomas M, Laura R, Hepner K, et al. Oncogenic human papillomavirus E6 proteins target the MAGI-2 and MAGI-3 proteins for degradation. Oncogene. 2002;21:5088-5096.
66. Lee SS, Glaunsinger B, Mantovani F, Banks L, Javier RT. Multi-PDZ domain protein MUPP1 is a cellular target for both adenovirus E4-ORF1 and high-risk papillomavirus type 18 E6 oncoproteins. J Virol. 2000;74:9680-9693.
67. Rey O, Lee S, Baluda MA, et al. The E7 oncoprotein of human papillomavirus type 16 interacts with F-actin in vitro and in vivo. Virology. 2000;268:372-381.
68. Werness BA, Levine AJ, Howley PM. Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science. 1990;248:76-79.
69. Park JS, Kim EJ, Lee JY, Sin HS, Namkoong SE, Um SJ. Functional inactivation of p73, a homolog of p53 tumor suppressor protein, by human papillomavirus E6 proteins. Int J Cancer. 2001;91:822-827.
70. Thomas M, Banks L. Human papillomavirus (HPV) E6 interactions with Bak are conserved amongst E6 proteins from high and low risk HPV types. J Gen Virol. 1999;80(Pt 6):1513-1517.
71. Filippova M, Parkhurst L, Duerksen-Hughes PJ. The human papillomavirus 16 E6 protein binds to Fas-associated death domain and protects cells from Fas-triggered apoptosis. J Biol Chem. 2004;279:25729-25744.
72. Filippova M, Song H, Connolly JL, Dermody TS, Duerksen-Hughes PJ. The human papillomavirus 16 E6 protein binds to tumor necrosis factor (TNF) R1 and protects cells from TNF-induced apoptosis. J Biol Chem. 2002;277:21730-21739.
73. Pim D, Massimi P, Dilworth SM, Banks L. Activation of the protein kinase B pathway by the HPV-16 E7 oncoprotein occurs through a mechanism involving interaction with PP2A. Oncogene. 2005;24:7830-7838.
74. Severino A, Abbruzzese C, Manente L, et al. Human papillomavirus-16 E7 interacts with Siva-1 and modulates apoptosis in HaCaT human immortalized keratinocytes. J Cell Physiol. 2007;212:118-125.
75. Bischof O, Nacerddine K, Dejean A. Human papillomavirus oncoprotein E7 targets the promyelocytic leukemia protein and circumvents cellular senescence via the Rb and p53 tumor suppressor pathways. Mol Cell Biol. 2005;25:1013-1024.
76. Schilling B, De-Medina T, Syken J, Vidal M, Munger K. A novel human DnaJ protein, hTid-1, a homolog of the Drosophila tumor suppressor protein Tid56, can interact with the human papillomavirus type 16 E7 oncoprotein. Virology. 1998;247:74-85.
77. Santer FR, Moser B, Spoden GA, Jansen-Durr P, Zwerschke W. Human papillomavirus type 16 E7 oncoprotein inhibits apoptosis mediated by nuclear insulin-like growth factor-binding protein-3 by enhancing its ubiquitin/proteasome-dependent degradation. Carcinogenesis. 2007;28:2511-2520.
78. Lu Z, Hu X, Li Y, et al. Human papillomavirus 16 E6 oncoprotein interferences with insulin signaling pathway by binding to tuberin. J Biol Chem. 2004;279:35664-35670.
79. Kuhne C, Banks L. E3-ubiquitin ligase/E6-AP links multicopy maintenance protein 7 to the ubiquitination pathway by a novel motif, the L2G box. J Biol Chem. 1998;273:34302-34309.
80. Jones DL, Alani RM, Munger K. The human papillomavirus E7 oncoprotein can uncouple cellular differentiation and proliferation in human keratinocytes by abrogating p21Cip1-mediated inhibition of cdk2. Genes Dev. 1997;11:2101-2111.
81. Zerfass-Thome K, Zwerschke W, Mannhardt B, Tindle R, Botz JW, Jansen-Durr P. Inactivation of the cdk inhibitor p27KIP1 by the human papillomavirus type 16 E7 oncoprotein. Oncogene. 1996;13:2323-2330.
82. Tommasino M, Adamczewski JP, Carlotti F, et al. HPV16 E7 protein associates with the protein kinase p33CDK2 and cyclin A. Oncogene. 1993;8:195-202.
83. Giarre M, Caldeira S, Malanchi I, Ciccolini F, Leao MJ, Tommasino M. Induction of pRb degradation by the human papillomavirus type 16 E7 protein is essential to efficiently overcome p16INK4a-imposed G1 cell cycle Arrest. J Virol. 2001;75:4705-4712.
84. Arroyo M, Bagchi S, Raychaudhuri P. Association of the human papillomavirus type 16 E7 protein with the S-phase-specific E2F-cyclin A complex. Mol Cell Biol. 1993;13:6537-6546.
85. Davies R, Hicks R, Crook T, Morris J, Vousden K. Human papillomavirus type 16 E7 associates with a histone H1 kinase and with p107 through sequences necessary for transformation. J Virol. 1993;67:2521-2528.
86. McIntyre MC, Ruesch MN, Laimins LA. Human papillomavirus E7 oncoproteins bind a single form of cyclin E in a complex with cdk2 and p107. Virology. 1996;215:73-82.
87. Dyson N, Howley PM, Munger K, Harlow E. The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science. 1989;243:934-937.
88. Srivenugopal KS, Ali-Osman F. The DNA repair protein, O-methylguanine-DNA methyltransferase is a proteolytic target for the E6 human papillomavirus oncoprotein. Oncogene. 2002;21:5940-5945.
89. Berezutskaya E, Bagchi S. The human papillomavirus E7 oncoprotein functionally interacts with the S4 subunit of the 26 S proteasome. J Biol Chem. 1997;272:30135-30140.
90. Zwerschke W, Mazurek S, Massimi P, Banks L, Eigenbrodt E, Jansen-Durr P. Modulation of type M2 pyruvate kinase activity by the human papillomavirus type 16 E7 oncoprotein. Proc Natl Acad Sci U S A. 1999;96:1291-1296.
91. Mileo AM, Piombino E, Severino A, Tritarelli A, Paggi MG, Lombardi D. Multiple interference of the human papillomavirus-16 E7 oncoprotein with the functional role of the metastasis suppressor Nm23-H1 protein. J Bioenerg Biomembr. 2006;38:215-225.
92. Favre-Bonvin A, Reynaud C, Kretz-Remy C, Jalinot P. Human papillomavirus type 18 E6 protein binds the cellular PDZ protein TIP-2/GIPC, which is involved in transforming growth factor beta signaling and triggers its degradation by the proteasome. J Virol. 2005;79:4229-4237.
93. Hampson L, Li C, Oliver AW, Kitchener HC, Hampson IN. The PDZ protein Tip-1 is a gain of function target of the HPV16 E6 oncoprotein. Int J Oncol. 2004;25:1249-1256.
94. Gao Q, Srinivasan S, Boyer SN, Wazer DE, Band V. The E6 oncoproteins of high-risk papillomaviruses bind to a novel putative GAP protein, E6TP1, and target it for degradation. Mol Cell Biol. 1999;19:733-744.
95. Li S, Labrecque S, Gauzzi MC, et al. The human papilloma virus (HPV)-18 E6 oncoprotein physically associates with Tyk2 and impairs Jak-STAT activation by interferon-alpha. Oncogene. 1999;18:5727-5737.
96. Jing M, Bohl J, Brimer N, Kinter M, Vande Pol SB. Degradation of tyrosine phosphatase PTPN3 (PTPH1) by association with oncogenic human papillomavirus E6 proteins. J Virol. 2007;81:2231-2239.
97. Gao Q, Kumar A, Srinivasan S, et al. PKN binds and phosphorylates human papillomavirus E6 oncoprotein. J Biol Chem. 2000;275:14824-14830.
98. Spitkovsky D, Hehner SP, Hofmann TG, Moller A, Schmitz ML. The human papillomavirus oncoprotein E7 attenuates NF-kappa B activation by targeting the Ikappa B kinase complex. J Biol Chem. 2002;277:25576-25582.
99. Ronco LV, Karpova AY, Vidal M, Howley PM. Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity. Genes Dev. 1998;12:2061-2072.
100. Gewin L, Myers H, Kiyono T, Galloway DA. Identification of a novel telomerase repressor that interacts with the human papillomavirus type-16 E6/E6-AP complex. Genes Dev. 2004;18:2269-2282.
101. Kumar A, Zhao Y, Meng G, et al. Human papillomavirus oncoprotein E6 inactivates the transcriptional coactivator human ADA3. Mol Cell Biol. 2002;22:5801-5812.
102. Gupta S, Takhar PP, Degenkolbe R, et al. The human papillomavirus type 11 and 16 E6 proteins modulate the cellcycle regulator and transcription cofactor TRIP-Br1. Virology. 2003;317:155-164.
103. Enzenauer C, Mengus G, Lavigne A, Davidson I, Pfister H, May M. Interaction of human papillomavirus 8 regulatory proteins E2, E6 and E7 with components of the TFIID complex. Intervirology. 1998;41:80-90.
104. Mendoza JA, Jacob Y, Cassonnet P, Favre M. Human papillomavirus type 5 E6 oncoprotein represses the transforming growth factor beta signaling pathway by binding to SMAD3. J Virol. 2006;80:12420-12424.
105. Lee DK, Kim BC, Kim IY, Cho EA, Satterwhite DJ, Kim SJ. The human papilloma virus E7 oncoprotein inhibits transforming growth factor-beta signaling by blocking binding of the Smad complex to its target sequence. J Biol Chem. 2002;277:38557-38564.
106. Patel D, Huang SM, Baglia LA, McCance DJ. The E6 protein of human papillomavirus type 16 binds to and inhibits co-activation by CBP and p300. EMBO J. 1999;18:5061-5072.
107. Bernat A, Avvakumov N, Mymryk JS, Banks L. Interaction between the HPV E7 oncoprotein and the transcriptional coactivator p300. Oncogene. 2003;22:7871-7881.
108. Gross-Mesilaty S, Reinstein E, Bercovich B, et al. Basal and human papillomavirus E6 oncoprotein-induced degradation of Myc proteins by the ubiquitin pathway. Proc Natl Acad Sci U S A. 1998;95:8058-8063.
109. Wang YW, Chang HS, Lin CH, Yu WC. HPV-18 E7 conjugates to c-Myc and mediates its transcriptional activity. Int J Biochem Cell Biol. 2007;39:402-412.
110. Dyson N, Guida P, Munger K, Harlow E. Homologous sequences in adenovirus E1A and human papillomavirus E7 proteins mediate interaction with the same set of cellular proteins. J Virol. 1992;66:6893-6902.
111. Massimi P, Pim D, Storey A, Banks L. HPV-16 E7 and adenovirus E1a complex formation with TATA box binding protein is enhanced by casein kinase II phosphorylation. Oncogene. 1996;12:2325-2330.
112. Nead MA, Baglia LA, Antinore MJ, Ludlow JW, McCance DJ. Rb binds c-Jun and activates transcription. EMBO J. 1998;17:2342-2352.
113. Campo-Fernandez B, Morandell D, Santer FR, Zwerschke W, Jansen-Durr P. Identification of the FHL2 transcriptional coactivator as a new functional target of the E7 oncoprotein of human papillomavirus type 16. J Virol. 2007;81:1027-1032.
114. Brehm A, Nielsen SJ, Miska EA, et al. The E7 oncoprotein associates with Mi2 and histone deacetylase activity to promote cell growth. EMBO J. 1999;18:2449-2458.
115. Prathapam T, Kuhne C, Banks L. The HPV-16 E7 oncoprotein binds Skip and suppresses its transcriptional activity. Oncogene. 2001;20:7677-7685.
116. Park JS, Kim EJ, Kwon HJ, Hwang ES, Namkoong SE, Um SJ. Inactivation of interferon regulatory factor-1 tumor suppressor protein by HPV E7 oncoprotein. Implication for the E7-mediated immune evasion mechanism in cervical carcinogenesis. J Biol Chem. 2000;275:6764-6769.
117. Luscher-Firzlaff JM, Westendorf JM, Zwicker J, et al. Interaction of the fork head domain transcription factor MPP2 with the human papilloma virus 16 E7 protein: enhancement of transformation and transactivation. Oncogene. 1999;18:5620-5630.
118. Barnard P, McMillan NA. The human papillomavirus E7 oncoprotein abrogates signaling mediated by interferon-alpha. Virology. 1999;259:305-313.
119. Jeong KW, Kim HZ, Kim S, Kim YS, Choe J. Human papillomavirus type 16 E6 protein interacts with cystic fibrosis transmembrane regulator-associated ligand and promotes E6-associated protein-mediated ubiquitination and proteasomal degradation. Oncogene. 2007;26:487-499.
120. Chen JJ, Reid CE, Band V, Androphy EJ. Interaction of papillomavirus E6 oncoproteins with a putative calcium-binding protein. Science. 1995;269:529-531.
121. Du M, Fan X, Hong E, Chen JJ. Interaction of oncogenic papillomavirus E6 proteins with fibulin-1. Biochem Biophys Res Commun. 2002;296:962-969.
122. Scheffner M, Huibregtse JM, Vierstra RD, Howley PM. The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell. 1993;75:495-505.
123. Matsumoto Y, Nakagawa S, Yano T, et al. Involvement of a cellular ubiquitin-protein ligase E6AP in the ubiquitin-mediated degradation of extensive substrates of high-risk human papillomavirus E6. J Med Virol. 2006;78:501-507.
124. Vambutas A, DeVoti J, Pinn W, Steinberg BM, Bonagura VR. Interaction of human papillomavirus type 11 E7 protein with TAP-1 results in the reduction of ATP-dependent peptide transport. Clin Immunol. 2001;101:94-99.
125. Nguyen CL, Eichwald C, Nibert ML, Munger K. Human papillomavirus type 16 E7 oncoprotein associates with the centrosomal component gamma-tubulin. J Virol. 2007;81:13533-13543.
126. Chan TF, Su TH, Yeh KT, et al. Mutational, epigenetic and expressional analyses of caveolin-1 gene in cervical cancers. Int J Oncol. 2003;23:599-604.
127. Chen CL, Liu SS, Ip SM, Wong LC, Ng TY, Ngan HY. E-cadherin expression is silenced by DNA methylation in cervical cancer cell lines and tumours. Eur J Cancer. 2003;39:517-523.
128. Cheung TH, Lo KW, Yim SF, et al. Epigenetic and genetic alternation of PTEN in cervical neoplasm. Gynecol Oncol. 2004;93:621-627.
129. Dong SM, Kim HS, Rha SH, Sidransky D. Promoter hypermethylation of multiple genes in carcinoma of the uterine cervix. Clin Cancer Res. 2001;7:1982-1986.
130. Feng Q, Balasubramanian A, Hawes SE, et al. Detection of hypermethylated genes in women with and without cervical neoplasia. J Natl Cancer Inst. 2005;97:273-282.
131. Ivanova T, Petrenko A, Gritsko T, et al. Methylation and silencing of the retinoic acid receptor-beta 2 gene in cervical cancer. BMC Cancer. 2002;2:4.
132. Ivanova T, Vinokurova S, Petrenko A, et al. Frequent hypermethylation of 5′ flanking region of TIMP-2 gene in cervical cancer. Int J Cancer. 2004;108:882-886.
133. Ivanova TA, Golovina DA, Zavalishina LE, et al. Up-regulation of expression and lack of 5′ CpG island hypermethylation of p16 INK4a in HPV-positive cervical carcinomas. BMC Cancer. 2007;7:47.
134. Jeong DH, Youm MY, Kim YN, et al. Promoter methylation of p16, DAPK, CDH1, and TIMP-3 genes in cervical cancer: correlation with clinicopathologic characteristics. Int J Gynecol Cancer. 2006;16:1234-1240.
135. Kang S, Kim J, Kim HB, et al. Methylation of p16INK4a is a non-rare event in cervical intraepithelial neoplasia. Diagn Mol Pathol. 2006;15:74-82.
136. Kang S, Kim JW, Kang GH, et al. Polymorphism in folate-and methionine-metabolizing enzyme and aberrant CpG island hypermethylation in uterine cervical cancer. Gynecol Oncol. 2005;96:173-180.
137. Kang S, Kim HS, Seo SS, Park SY, Sidransky D, Dong SM. Inverse correlation between RASSF1A hypermethylation, KRAS and BRAF mutations in cervical adenocarcinoma. Gynecol Oncol. 2007;105:662-666.
138. Kang S, Kim JW, Kang GH, et al. Comparison of DNA hypermethylation patterns in different types of uterine cancer: cervical squamous cell carcinoma, cervical adenocarcinoma and endometrial adenocarcinoma. Int J Cancer. 2006;118:2168-2171.
139. Kim NR, Lin Z, Kim KR, Cho HY, Kim I. Epstein-Barr virus and p16INK4A methylation in squamous cell carcinoma and precancerous lesions of the cervix uteri. J Korean Med Sci. 2005;20:636-642.
140. Kim TY, Lee HJ, Hwang KS, et al. Methylation of RUNX3 in various types of human cancers and premalignant stages of gastric carcinoma. Lab Invest. 2004;84:479-484.
141. Kitkumthorn N, Yanatatsanajit P, Kiatpongsan S, et al. Cyclin A1 promoter hypermethylation in human papillomavirus-associated cervical cancer. BMC Cancer. 2006;6:55.
142. Kuzmin I, Liu L, Dammann R, et al. Inactivation of RAS association domain family 1A gene in cervical carcinomas and the role of human papillomavirus infection. Cancer Res. 2003;63:1888-1893.
143. Lai HC, Lin YW, Chang CC, et al. Hypermethylation of 2 consecutive tumor suppressor genes, BLU and RASSF1A, located at 3p213 in cervical neoplasias. Gynecol Oncol. 2007;104:629-635.
144. Lea JS, Coleman R, Kurien A, et al. Aberrant p16 methylation is a biomarker for tobacco exposure in cervical squamous cell carcinogenesis. Am J Obstet Gynecol. 2004;190:674-679.
145. Li J, Zhang Z, Bidder M, et al. IGSF4 promoter methylation and expression silencing in human cervical cancer. Gynecol Oncol. 2005;96:150-158.
146. Lin Z, Gao M, Zhang X, et al. The hypermethylation and protein expression of p16 INK4A and DNA repair gene O6-methylguanine-DNA methyltransferase in various uterine cervical lesions. J Cancer Res Clin Oncol. 2005;131:364-370.
147. Narayan G, Goparaju C, Arias-Pulido H, et al. Promoter hypermethylation-mediated inactivation of multiple Slit-Robo pathway genes in cervical cancer progression. Mol Cancer. 2006;5:16.
148. Narayan G, Arias-Pulido H, Koul S, et al. Frequent promoter methylation of CDH1, DAPK, RARB, and HIC1 genes in carcinoma of cervix uteri: its relationship to clinical outcome. Mol Cancer. 2003;2:24.
149. Nuovo GJ, Plaia TW, Belinsky SA, Baylin SB, Herman JG. In situ detection of the hypermethylation-induced inactivation of the p16 gene as an early event in oncogenesis. Proc Natl Acad Sci U S A. 1999;96:12754-12759.
150. Park SY, Kim BH, Kim JH, et al. Methylation profiles of CpG island loci in major types of human cancers. J Korean Med Sci. 2007;22:311-317.
151. Ren CC, Miao XH, Yang B, Zhao L, Sun R, Song WQ. Methylation status of the fragile histidine triad and E-cadherin genes in plasma of cervical cancer patients. Int J Gynecol Cancer. 2006;16:1862-1867.
152. Seng TJ, Low JS, Li H, et al. The major 8p22 tumor suppressor DLC1 is frequently silenced by methylation in both endemic and sporadic nasopharyngeal, esophageal, and cervical carcinomas, and inhibits tumor cell colony formation. Oncogene. 2007;26:934-944.
153. Shigematsu H, Suzuki M, Takahashi T, et al. Aberrant methylation of HIN-1 (high in normal-1) is a frequent event in many human malignancies. Int J Cancer. 2005;113:600-604.
154. Shivapurkar N, Toyooka S, Toyooka KO, et al. Aberrant methylation of trail decoy receptor genes is frequent in multiple tumor types. Int J Cancer. 2004;109:786-792.
155. Steenbergen RD, Kramer D, Braakhuis BJ, et al. TSLC1 gene silencing in cervical cancer cell lines and cervical neoplasia. J Natl Cancer Inst. 2004;96:294-305.
156. Takahashi T, Suzuki M, Shigematsu H, et al. Aberrant methylation of Reprimo in human malignancies. Int J Cancer. 2005;115:503-510.
157. Virmani AK, Muller C, Rathi A, Zoechbauer-Mueller S, Mathis M, Gazdar AF. Aberrant methylation during cervical carcinogenesis. Clin Cancer Res. 2001;7:584-589.
158. Widschwendter A, Gattringer C, Ivarsson L, et al. Analysis of aberrant DNA methylation and human papillomavirus DNA in cervicovaginal specimens to detect invasive cervical cancer and its precursors. Clin Cancer Res. 2004;10:3396-3400.
159. Widschwendter A, Muller HM, Hubalek MM, et al. Methylation status and expression of human telomerase reverse transcriptase in ovarian and cervical cancer. Gynecol Oncol. 2004;93:407-416.
160. Wong YF, Chung TK, Cheung TH, et al. Methylation of p16INK4A in primary gynecologic malignancy. Cancer Lett. 1999;136:231-235.
161. Wu Q, Shi H, Suo Z, Nesland JM. 5′-CpG island methylation of the FHIT gene is associated with reduced protein expression and higher clinical stage in cervical carcinomas. Ultrastruct Pathol. 2003;27:417-422.
162. Yang HJ, Liu VW, Wang Y, Tsang PC, Ngan HY. Differential DNA methylation profiles in gynecological cancers and correlation with clinico-pathological data. BMC Cancer. 2006;6:212.
163. Yang HJ, Liu VW, Wang Y, et al. Detection of hypermethylated genes in tumor and plasma of cervical cancer patients. Gynecol Oncol. 2004;93:435-440.
164. Yu MY, Tong JH, Chan PK, et al. Hypermethylation of the tumor suppressor gene RASSFIA and frequent concomitant loss of heterozygosity at 3p21 in cervical cancers. Int J Cancer. 2003;105:204-209.
165. Zhang Z, Joh K, Yatsuki H, et al. Retinoic acid receptor beta2 is epigenetically silenced either by DNA methylation or repressive histone modifications at the promoter in cervical cancer cells. Cancer Lett. 2007;247:318-327.
166. Zhang Z, Huettner PC, Nguyen L, et al. Aberrant promoter methylation and silencing of the POU2F3 gene in cervical cancer. Oncogene. 2006;25:5436-5445.
167. Nakashima R, Fujita M, Enomoto T, et al. Alteration of p16 and p15 genes in human uterine tumours. Br J Cancer. 1999;80:458-467.
168. Tripathi A, Banerjee S, Roy A, Roychowdhury S, Panda CK. Alterations of the P16 gene in uterine cervical carcinoma from Indian patients. Int J Gynecol Cancer. 2003;13:472-479.
169. Cohen Y, Singer G, Lavie O, Dong SM, Beller U, Sidransky D. The RASSF1A tumor suppressor gene is commonly inactivated in adenocarcinoma of the uterine cervix. Clin Cancer Res. 2003;9:2981-2984.
170. Reesink-Peters N, Wisman GB, Jeronimo C, et al. Detecting cervical cancer by quantitative promoter hypermethylation assay on cervical scrapings: a feasibility study. Mol Cancer Res. 2004;2:289-295.
171. Gustafson KS, Furth EE, Heitjan DF, Fansler ZB, Clark DP. DNA methylation profiling of cervical squamous intraepithelial lesions using liquid-based cytology specimens: an approach that utilizes receiver-operating characteristic analysis. Cancer. 2004;102:259-268.