Regulation of E6 and E7 Oncogene Transcription

  • Frank Rösl
  • Elisabeth Schwarz


Expression of the viral oncogenes E6 and E7 is fundamental to HPV-associated carcinogenesis. The multistep progression of a persistent infection by HPV16 or HPV18 or another “high risk” HPV type from a clinically inconspicuous state to a detectable precursor lesion and eventually to a carcinoma is thought to be driven mainly by the oncoproteins E6 and E7. Furthermore, the maintenance of the malignant phenotype also requires the continuous expression of the HPV oncogenes.


Cervical Cancer Upstream Regulatory Region Retinoid Receptor Cervical Carcinoma Cell Line Cellular Transcription Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Crum CP, Nuovo G, Friedman D et al. Accumulation of RNA homologous to human papillomavirus type 16 open reading frames in genital precancers. J Virol 1988; 62: 84–90.PubMedGoogle Scholar
  2. 2.
    Durst M, Glitz D, Schneider A et al. Human papillomavirus type 16 (HPV16) gene expression and DNA replication in cervical neoplasia: analysis by in situ hybridization. Virology 1992; 189: 132–140.PubMedCrossRefGoogle Scholar
  3. 3.
    Stoler MH, Rhodes CR, Whitbeck A et al. Human papillomavirus type 16 and 18 gene expression in cervical neoplasias. Hum Pathol 1992; 23: 117–128.PubMedCrossRefGoogle Scholar
  4. 4.
    Crum CP, Symbula M, Ward BE. Topography of early HPV16 transcription in high-grade genital precancers. Am J Pathol 1989; 134: 1183–1188.PubMedGoogle Scholar
  5. 5.
    Schneider-Gädicke A, Schwarz E. Different human cervical carcinoma cell lines show similar transcription patterns of human papillomavirus type 18 early genes. EMBO J 1986; 5: 2285–2292.PubMedGoogle Scholar
  6. 6.
    Sherman L, Alloul N, Golan I et al. Expression and splicing patterns of human papillomavirus type 16 mRNAs in precancerous lesions and carcinomas of the cervix, in human keratinocytes immortalized by HPV16, and in cell lines established from cervical cancers. Int J Cancer 1992; 50: 356–364.PubMedCrossRefGoogle Scholar
  7. 7.
    Roeder RG. The role of general initiation factors in transcription by RNA polymerase II. Trends Biochem Sci 1996; 21: 327–335.PubMedGoogle Scholar
  8. 8.
    Chao DM, Young RA. Activation without a vital ingredient. Nature 1996; 383: 119–120.PubMedCrossRefGoogle Scholar
  9. 9.
    Koleske AJ, Young RA. The RNA polymerase II holoenzyme and its implication for gene regulation. Trends Biochem Sci 1995; 20: 113–116.PubMedCrossRefGoogle Scholar
  10. 10.
    Struhl K. Chromatin structure and RNA polymerase II connection: implications for transcription. Cell 1996; 84: 179–182.PubMedCrossRefGoogle Scholar
  11. 11.
    Goodrich JA, Cutler G, Tjian R. Contacts in context: promoter specificity and macromolecular interactions in transcription. Cell 1996; 84: 825–830.PubMedCrossRefGoogle Scholar
  12. 12.
    Cowell IG. Repression versus activation in the control of gene transcription. Trends Biochem Sci 1994; 19: 38–42.PubMedCrossRefGoogle Scholar
  13. 13.
    Gloss B, Bernhard HU, Seedorf K et al. The upstream regulatory region of the human papillomavirus-16 contains an E2 protein-independent enhancer which is specific for cervical carcinoma cells and regulated by glucocorticoid hormones. EMBO J 1987; 6: 3735–3743.PubMedGoogle Scholar
  14. 14.
    Cripe TP, Alderborn A, Anderson RD et al. Transcriptional activation of the human papillomavirus-16 P97 promoter by an 88-nucleotide enhancer containing distinct cell-dependent and AP-1-responsive modules. The New Biologist 1990; 2: 450–463.PubMedGoogle Scholar
  15. 15.
    Garcia-Carranca A, Thierry F, Yaniv M. Interplay of viral and cellular proteins along the long control region of human papillomavirus type 18. J Virol 1988; 62: 4321–4330.PubMedGoogle Scholar
  16. 16.
    Gius D, Grossman S, Bedell MA et al. Inducible and constitutive enhancer domains in the noncoding region of human papillomavirus type 18. J Virol 1988; 62: 665–672.PubMedGoogle Scholar
  17. 17.
    Hoppe-Seyler F, Butz K. A novel cis-stimulatory element maps to the 5’ portion of the human papillomavirus type 18 upstream regulatory region and is functionally dependent on a sequence-aberrant Sp1 binding site. J Gen Virol 1993; 74: 281–286.PubMedCrossRefGoogle Scholar
  18. 18.
    Ham J, Dostatni N, Gauthier JM et al. The papillomavirus E2 protein: a factor with many talents. Trends Biochem Sci 1991; 16: 440–444.PubMedCrossRefGoogle Scholar
  19. 19.
    Howley PM. Papillomavirinae: the viruses and their replication. In: Fields BN et al, eds. Virology. 3rd ed. Philadelphia: Lippincott-Raven Publishers, 1996: 2045–2076.Google Scholar
  20. 20.
    McBride AA, Romanczuk H, Howley PM. The papillomavirus E2 regulatory proteins. J Biol Chem 1991; 266: 18411–18414.PubMedGoogle Scholar
  21. 21.
    O’Connor MJ, Chan S-Y, Bernard H-U. Transcription factor binding sites in the long control region of genital HPVs. In: Myers G et al, eds. Human Papillomaviruses 1995. A Compilation and Analysis of Nucleic Acid and Amino Acid Sequences. Part III. Los Alamos: Los Alamos National Laboratory, 1995: 47–57.Google Scholar
  22. 22.
    Thierry F, Yaniv M. The BPV1–E2 trans-acting protein can act either as an activator or a repressor of the HPV18 regulatory region. EMBO J 1987; 6: 3391–3397.PubMedGoogle Scholar
  23. 23.
    Bernard BA, Bailly C, Lenoir MC et al. The human papillomavirus type 18 (HPV18) E2 product is a repressor of the HPV18 regulatory region in human keratinocytes. J Virol 1989; 63: 4317–4324.PubMedGoogle Scholar
  24. 24.
    Romanczuk H, Thierry F, Howley PM. Mutational analysis of cis elements involved in E2 modulation of human papillomavirus type 16 P97 and type 18 P105 promoters. J Virol 1990; 64: 2849–2859.PubMedGoogle Scholar
  25. 25.
    Dong XP, Stubenrauch F, Beyer-Finkler E et al. Prevalence of deletions of YY-1 binding sites in episomal HPV16 DNA from cervical cancer. Int J Cancer 1994; 58: 803–808.PubMedCrossRefGoogle Scholar
  26. 26.
    Romanczuk H, Howley PM. Disruption of either the El or the E2 regulatory gene of human papillomavirus type 16 increases viral immortalization capacity. Proc Natl Acad Sci USA 1992; 89: 3159–3163.PubMedCrossRefGoogle Scholar
  27. 27.
    Tan SH, Leong LE, Walker PA et al. The human papillomavirus type 16 E2 transcription factor binds with low cooperativity to two flanking sites and represses the E6 promoter through displacement of Spl and TFIID. J Virol 1994; 68: 11–20.Google Scholar
  28. 28.
    Storey A, Greenfield I, Banks L et al. Lack of immortalizing activity of a human papillomavirus type 16 variant DNA with a mutation in the E2 gene isolated from normal human cervical keratinocytes. Oncogene 1992; 7: 459–465.PubMedGoogle Scholar
  29. 29.
    Bouvard V, Storey A, Pim D et al. Characterization of the human papillomavirus E2 protein: evidence of trans-activation and trans-repression in cervical keratinocytes. EMBO J 1994; 13: 5451–5459.PubMedGoogle Scholar
  30. 30.
    Ushikai M, Lace MJ, Yamakawa Y et al. Trans activation by the full-length E2 proteins of human papillomavirus type 16 and bovine papillomavirus type 1 in vitro and in vivo: cooperation with activation domains of cellular transcription factors. J Virol 1994; 68: 6655–6666.PubMedGoogle Scholar
  31. 31.
    Etscheid BG, Foster SA, Galloway DA. The E6 protein of human papillomavirus type 16 functions as a transcriptional repressor in a mechanism independent of the tumor suppressor protein p53. Virology 1994; 205: 583–585.PubMedCrossRefGoogle Scholar
  32. 32.
    Akutsu N, Shirasawa H, Asano T et al. p53-dependent and -independent transactivation by the E6 protein of human papillomavirus type 16. J Gen Virol 1996; 77: 459–463.PubMedCrossRefGoogle Scholar
  33. 33.
    Desaintes C, Hallez S, van Alphen P et al. Transcriptional activation of several heterologous promoters by E6 protein of human papillomavirus type 16. J Virol 1992; 66: 325–333.PubMedGoogle Scholar
  34. 34.
    Lamberti C, Morrissey LC, Grossman SR et al. Transcriptional activation by the papillomavirus E6 zinc finger protein. EMBO J 1990; 9: 1907–1913.PubMedGoogle Scholar
  35. 35.
    Sedman SA, Barbosa MS, Vass WC et al. The full-length E6 protein of human papillomavirus type 16 has transforming and trans-acti- vating activities and cooperates with E7 to immortalize keratinocytes in culture. J Virol 1991; 65: 4860–4866.PubMedGoogle Scholar
  36. 36.
    Carlotti F, Crawford L. Trans-activation of the adenovirus E2 promoter by human papillomavirus type 16 E7 is mediated by retinoblastoma-dependent and -independent pathways. J Gen Virol 1993; 74: 2479–2486.PubMedCrossRefGoogle Scholar
  37. 37.
    Wong HK, Ziff EB. The human papillomavirus type 16 E7 protein complements adenovirus type 5 E1A amino-terminus-dependent transactivation of adenovirus type 5 early genes and increases ATF and Oct-1 DNA binding activity. J Virol 1996; 70: 332–340.PubMedGoogle Scholar
  38. 38.
    Massimi P, Pim D, Storey A et al. HPV 16 E7 and adenovirus Ela complex formation with TATA box binding protein is enhanced by casein kinase II phosphorylation. Oncogene 1996; 12: 2325–2330PubMedGoogle Scholar
  39. 39.
    Mazzarelli JM, Atkins GB, Geisberg JV et al. The viral oncoproteins Ad5 Ela, HPV16 E7 and SV40 TAg bind a common region of the TBP-associated factor-110. Oncogene 1995; 11: 1859–1864.PubMedGoogle Scholar
  40. 40.
    Antinore MJ, Birrer MJ, Patel D et al. The human papillomavirus type 16 E7 gene product interacts with and trans-activates the AP1 family of transcription factors. EMBO J 1996; 15: 1950–1960.PubMedGoogle Scholar
  41. 41.
    Gloss B, Chong T, Bernhard HU. Numerous nuclear proteins bind the long control region of human papillomavirus type 16: a subset of 6 of 23 DNase I- protected segments coincide with the location of the cell-type-specific enhancer. J Virol 1989; 63: 1142–1152.PubMedGoogle Scholar
  42. 42.
    Nakshatri H, Pater MM, Pater A. Ubiquitous and cell-type specific protein interactions with papillomavirus type 16 and type 18 enhancers. Virology 1990; 178: 92–103.PubMedCrossRefGoogle Scholar
  43. 43.
    Butz K, Hoppe-Seyler F. Transcriptional control of human papillomavirus (HPV) oncogene expression: composition of the HPV type 18 upstream regulatory region. J Virol 1993; 67: 6476–6486.PubMedGoogle Scholar
  44. 44.
    Hoppe-Seyler F, Butz K. Cellular control of human papillomavirus oncogene transcription. Mol Carcinogenesis 1994; 10: 134–141.CrossRefGoogle Scholar
  45. 45.
    Angel P, Karin M. The role of jun, fos and the AP-1 complex in cell-proliferation and transformation. Biochem Biophys Acta 1991; 1072: 129–157.PubMedGoogle Scholar
  46. 46.
    Rutberg SE, Saez E, Glick A et al. Differentiation of mouse keratinocytes is accompanied by PKC-dependent changes in AP-1 proteins. Oncogene 1996; 13: 167–176.PubMedGoogle Scholar
  47. 47.
    Schenk H, Klein M, Erdbrügger W et al. Distinct effects of thioredoxin and antioxidants on the activation of transcription factor NF-xß and AP-1. Proc Natl Acad Sci USA 1994; 91: 1672–1676.PubMedCrossRefGoogle Scholar
  48. 48.
    Thierry F, Spyrou G, Yaniv M et al. Two AP-1 sites binding junB are essential for human papillomavirus type 18 transcription in keratinocytes. J Virol 1992; 66: 3740–3748.PubMedGoogle Scholar
  49. 49.
    Offord EA, Beard P. A member of the activator protein 1 family found in keratinocytes but not in fibroblasts required for transcription from a human papillomavirus type 18 promoter. J Virol 1990; 64: 4792–4798.PubMedGoogle Scholar
  50. 50.
    Rösl F, Das BC, Lengert M et al. Antioxidant-induced changes of the AP-1 transcription complex are paralleled by a selective suppression of human papillomavirus transcription. J Virol 1997; 71: 362–370.PubMedGoogle Scholar
  51. 51.
    Choo K-B, Huang C-J, Chen C-M et al. Jun-B oncogene aberrations in cervical cancer cell lines. Cancer Letters 1995; 93: 249–253.PubMedCrossRefGoogle Scholar
  52. 52.
    Shrivastava A, Calame K. An analysis of genes regulated by the multifunctional transcriptional regulator Yin Yang-1. Nucleic Acids Res 1994; 22: 5151–5155.PubMedCrossRefGoogle Scholar
  53. 53.
    Bauknecht T, Angel P, Royer H-D et al. Identification of a negative regulatory domain in the human papillomavirus type 18 promoter: interaction with the transcriptional repressor YY1. EMBO J 1992; 11: 4607–4617.PubMedGoogle Scholar
  54. 54.
    May M, Dong X-P, Beyer-Finkler E et al. The E6/E7 promoter of extrachromosomal HPV16 DNA in cervical cancers escapes from cellular repression by mutation of target sequences for YY1. EMBO J 1994; 13: 1460–1466.PubMedGoogle Scholar
  55. 55.
    Bauknecht T, Jundt F, Herr I et al. A switch region determines the cell type-specific positive or negative action of YY1 on the activity of the human papillomvirus type 18 promoter. J Virol 1995; 69: 1–12.PubMedGoogle Scholar
  56. 56.
    Bauknecht T. See RH, Shi Y. A novel C/EBP 13-YY1 complex controls the cell-type-specific activity of the human papillomavirus type 18 upstream regulatory region. J Virol 1996; 70: 7695–7705.PubMedGoogle Scholar
  57. 57.
    Jundt F, Herr I, Angel P et al. Transcriptional control of human papillomavirus type 18 oncogene expression in different cell lines: role of transcription factor YY1. Virus Genes 1995; 11: 53–58.PubMedCrossRefGoogle Scholar
  58. 58.
    O’Connor MJ, Tan SH, Tan CH et al. YY1 represses human papillomavirus type 16 transcription by quenching AP-1 activity. J Virol 1996; 70: 6529–6539.PubMedGoogle Scholar
  59. 59.
    Akira S, Issiki H, Sugita T et al. A nuclear factor for IL-6 expression (NF-IL6) is a member of a C/EBP family. EMBO J 1990; 9: 1897–1906.PubMedGoogle Scholar
  60. 60.
    Kyo S, Inoue M, Nishio Y et al. NF-IL6 represses early gene expression of human papillomavirus type 16 through binding to the noncoding region. J Virol 1993; 67: 1058–1066.PubMedGoogle Scholar
  61. 61.
    Wang H, Liu K, Yuan F et al. C/EBP-13 is a negative regulator of human papillomavirus type 11 in keratinocytes. J Virol 1996; 70: 4839–4844.PubMedGoogle Scholar
  62. 62.
    Klampfer L, Lee TH, Hsu W, Vilcek J, Chen-Kiang S. NF-IL6 and AP-1 cooperatively modulate the activation of the TSG-1 gene by tumor necrosis factor a and interleukin-1. Mol Cell Biol 1994; 14: 6561–6569.PubMedGoogle Scholar
  63. 63.
    Hsu W, Kerppola TK, Chen PL et al. Fos and Jun repress transcription activation by NF-IL6 through association at the basic zipper region. Mol Cell Biol 1994; 14: 268–276.PubMedGoogle Scholar
  64. 64.
    Gloss B, Bernhard HU. The E6/E7 promoter of human papillomavirus type 16 is activated in the absence of E2 proteins by a sequence-aberrant Spi distal element. J Virol 1990; 64: 5577–5584.PubMedGoogle Scholar
  65. 65.
    Demeret C, Yaniv M, Thierry F. The E2 transcriptional repressor can compensate for Spi activation of the human papillomavirus type 18 early promoter. J Virol 1994; 68: 7075–7082.PubMedGoogle Scholar
  66. 66.
    Hoppe-Seyler F, Butz K. Activation of human papilloma virus type 18 E6–E7 oncogene expression by transcription factor Spl. Nucleic Acids Res 1992; 20: 6701–6706.PubMedCrossRefGoogle Scholar
  67. 67.
    Evans RM. The steroid and thyroid hormone receptor superfamily. Science 1988; 240: 889–895.PubMedCrossRefGoogle Scholar
  68. 68.
    Beato M, Herrlich P, Schütz G. Steroid hormone receptors: many actors in search of a plot. Cell 1995; 83: 851–857.PubMedCrossRefGoogle Scholar
  69. 69.
    Mangelsdorf DJ, Umesono K, Evans RM. The retinoid receptors. In: Sporn MB, Roberts AB, Goodman DS, eds. The Retinoid Receptors: Biology, Chemistry, and Medicine. New York: Raven Press, 1994: 319–349.Google Scholar
  70. 70.
    Chan WK, Klock G, Bernard H-U. Progesterone and glucocorticoid response elements occur in the long control regions of several human papillomaviruses involved in anogenital neoplasia. J Virol 1989; 63: 3261–3269.PubMedGoogle Scholar
  71. 71.
    Mittal R, Pater A, Pater MM. Multiple human papillomavirus type 16 glucocorticoid response elements functional for transformation, transient expression, and DNA-protein interactions. J Virol 1993; 67: 5656–5659.PubMedGoogle Scholar
  72. 72.
    Medina-Martinez O, Morales-Peza N, Yaniv M et al. A single element mediates glucocorticoid hormone response of HPV18 with no functional interactions with AP1 or hbrm. Virology 1996; 217: 392–396.PubMedCrossRefGoogle Scholar
  73. 73.
    Pater MM, Mittal R, Pater A. Role of steroid hormones in potentiating transformation of cervical cells by human papillomaviruses. Trends Genet 1994; 2: 229–235.Google Scholar
  74. 74.
    Bartsch D, Boye B, Baust C et al. Retinoic acid-mediated repression of human papillomavirus 18 transcription and different ligand regulation of the retinoic acid receptor gene in nontumorigenic and tumorigenic HeLa hybrid cells. EMBO J 1992; 11: 2283–2291.PubMedGoogle Scholar
  75. 75.
    Schüle R, Evans RM. Cross-coupling of signal transduction pathways: zinc finger meets leucine zipper. Trends Genet 1991; 7: 377–381.PubMedGoogle Scholar
  76. 76.
    Mack DH, Laimins LA. A keratinocyte-specific transcription factor, KRF-1, interacts with AP-1 to activate expression of human papillomavirus type 18 in squamous epithelial cells. Proc Natl Acad Sci USA 1991; 88: 9102–9106.PubMedCrossRefGoogle Scholar
  77. 77.
    Rosenfeld MG. POU-domain transcription factors: pou-er-ful developmental regulators. Genes & Development 1991; 5: 897–907.CrossRefGoogle Scholar
  78. 78.
    Hoppe-Seyler F, Butz K, zur Hausen H. Repression of the human papillomavirus type 18 enhancer by the cellular transcription factor Oct-1. J Virol 1991; 65: 5613–5618.PubMedGoogle Scholar
  79. 79.
    Chong T, Apt D, Gloss B et al. The enhancer of human papillomavirus type 16: binding sites for the ubiquitous transcription factors oct-1, NFA, TEF-2, NF1, and AP-1 participate in epithelial cell-specific transcription. J Virol 1991; 65: 5933–5943.PubMedGoogle Scholar
  80. 80.
    O’Connor M, Bernhard H-U. Oct-1 activates the epithelial-specific enhancer of human papillomavirus type 16 via a synergistic interaction with NFI at a conserved composite regulatory element. Virology 1995; 207: 77–88.PubMedCrossRefGoogle Scholar
  81. 81.
    Sibbet GJ, Cuthill S, Campo MS. The enhancer in the long control region of human papillomavirus type 16 is up-regulated by PEF-1 and down-regulated by Oct-1. J Virol 1995; 69: 4006–4011.PubMedGoogle Scholar
  82. 82.
    List HJ, Patzel V, Zeidler U et al. Methylation sensitivity of the enhancer from the human papillomavirus type 16. J Biol Chem 1994; 269: 11902–11911.PubMedGoogle Scholar
  83. 83.
    Yukawa K, Butz K, Yasui T et al. Regulation of human papillomavirus transcription by the differentiation-dependent epithelial factor Epoc1/skn-la. J Virol 1996; 70: 10–16.PubMedGoogle Scholar
  84. 84.
    Pederson DS, Heintz NH. Transcription factors and DNA replication. R.G. Landes Company, Austin; 1994.Google Scholar
  85. 85.
    Faus I, Hsu HJ, Fuchs E. Oct-6: a regulator of keratinocyte gene expression in stratified squamous epithelia. Mol Cell Biol 1994; 14: 3263–3275.PubMedGoogle Scholar
  86. 86.
    Apt D, Liu Y, Bernhard H-U. Cloning and functional analysis of spliced isoforms of human nuclear factor I-X: interference with transcriptional activation by NFI/CTF in a cell-type specific manner. Nucleic Acids Res 1994; 19: 3825–3833.CrossRefGoogle Scholar
  87. 87.
    Chong T, Chan W, Bernhard H.-U. Transcriptional activation of human papillomavirus 16 by nuclear factor I, API, steroid receptors and a possibly novel transcription factor, PVF: a model for the composition of genital papillomavirus enhancers. Nucleic Acids Res 1990; 18: 465–470.PubMedCrossRefGoogle Scholar
  88. 88.
    Apt D, Chong T, Liu Y et al. Nuclear factor I and epithelial cell-specific transcription of human papillomavirus 16. J Virol 1993; 67: 4455–4463.PubMedGoogle Scholar
  89. 89.
    Ishiji T, Lace MJ, Parkkinen S et al. Transcriptional enhancer factor (TEF)-1 and its cell-specific coactivator activate human papillomavirus-16 E6 and E7 oncogene transcription in keratinocytes and cervical carcinoma cells. EMBO J 1992; 11: 2271–2281.PubMedGoogle Scholar
  90. 90.
    Durst M, Kleinheinz A, Hotz M et al. The physical state of human papillomavirus type 16 DNA in benign and malignant genital tumors. J Gen Virol 1985; 66: 1515–1522.PubMedCrossRefGoogle Scholar
  91. 91.
    Choo KB, Pan CC, Han SM. Integration of human papillomavirus type 16 into cellular DNA of cervical carcinoma: preferential deletion of the E2 gene and invariable retention of the long control region and the E6/E7 open reading frames. Virology 1987; 161: 259–261.PubMedCrossRefGoogle Scholar
  92. 92.
    Cullen AP, Reid R, Campion M et al. Analysis of the physical state of different human papillomavirus DNAs in intraepithelial and invasive cervical neoplasm. J Virol 1991; 65: 606–612.PubMedGoogle Scholar
  93. 93.
    Schneider-Manoury S, Croissant O, Orth G. Integration of human papillomavirus type 16 DNA sequences: a possible early event in the progression of genital tumors. J Virol 1987; 61: 3295–3298.Google Scholar
  94. 94.
    Daniel B, Mukherjee G, Seshadri L et al. Changes in the physical state and expression of human papillomavirus type 16 in the progression of cervical intraepithelial neoplasia lesion analyzed by PCR. J Gen Virol 1995; 76: 2589–2593.PubMedCrossRefGoogle Scholar
  95. 95.
    Schwarz E, Freese K, Gissmann L et al. Structure and transcription of human papillomvirus sequences in cervical carcinoma cells. Nature 1985; 314: 111–114.PubMedCrossRefGoogle Scholar
  96. 96.
    Baker CC, Phelps WC, Lindgren V et al. Structural and transcriptional analysis of human papillomavirus type 16 in cervical carcinoma cell lines. J Virol 1987; 61: 962–971.PubMedGoogle Scholar
  97. 97.
    Wilczynski SP, Pearlman L, Walker J. Identification of HPV16 early genes retained in cervical carcinomas. Virology 1988; 166: 624–627.PubMedCrossRefGoogle Scholar
  98. 98.
    Sang B-C, Barbosa MS. Increased E6/E7 transcription in HPV18 immortalized human keratinocytes results from inactivation of E2 and additional cellular events. Virology 1992; 189: 448–455.PubMedCrossRefGoogle Scholar
  99. 99.
    Schwarz A, Schneider-Gaedicke A, zur Hausen H. Human papillomaviruses type-18 transcription in cervical carcinoma cell lines and in human cell hybrids. In: Steinberg BM et al, eds. Papillomaviruses. Cancer Cells 5. Cold Spring Harbor Laboratory, 1987: 47–53.Google Scholar
  100. 100.
    El Awady MK, Kaplan JB, O’Brien SJ et al. Molecular analysis of integrated human papillomavirus 16 sequences in the cervical carcinoma cell line SiHa. Virology 1987; 159: 389–398.PubMedCrossRefGoogle Scholar
  101. 101.
    Jeon S, Lambert PF. Integration of human papillomavirus type 16 into the human genome leads to increased stability of E6 and E7 mRNAs: implications for cervical carcinogenesis. Proc Natl Acad Sci USA 1995; 92: 1654–1658.PubMedCrossRefGoogle Scholar
  102. 102.
    Liu Z, Ghai J, Ostrow RS et al. The expression levels of the human papillomavirus type 16 E7 correlate with its transformation potential. Virology 1995; 207: 260–270.PubMedCrossRefGoogle Scholar
  103. 103.
    Elgin SCR. Anatomy of hypersensitive sites. Nature 1984; 309: 213–214.PubMedCrossRefGoogle Scholar
  104. 104.
    Rohdewohld H, Weiher H, Reik W et al. Retrovirus integrations and chromatin structure: Moloney murine leukemia provirus integration sites map near DNAse I-hypersensitive sites. J Virol 1987; 61: 336–343.PubMedGoogle Scholar
  105. 105.
    Rösl F, Westphal E-M, zur Hausen H. Chromatin structure and transcriptional regulation of human papillomavirus type 18 DNA in HeLa cells. Mol Carcinogenesis 1989; 2: 72–80.CrossRefGoogle Scholar
  106. 106.
    Inagaki Y, Tsunokawa Y, Takebe N et al. Nucleotide sequences of cDNAs for human papillomavirus type 18 transcripts in HeLa cells. 1988; J Virol 62: 1640–1646.Google Scholar
  107. 107.
    Bauer-Hofmann R, Borghouts C, Auvinen E et al. Genomic cloning and characterization of the nonoccupied allele corresponding to the integration site of human papillomavirus type 16 DNA in the cervical cancer cell line SiHa. Virology 1996; 217: 33–41.PubMedCrossRefGoogle Scholar
  108. 108.
    von Knebel Doeberitz M, Bauknecht T, Bartsch D et al. Influence of chromosomal integration on glucocorticoid-regulated transcription of growth-stimulating papillomavirus genes E6 and E7 in cervical carcinoma cells. Proc Natl Acad Sci USA 1991; 88: 1411–1415.PubMedCrossRefGoogle Scholar
  109. 109.
    Holliday R. The inheritance of epigenetic defects. Science 1987; 238: 163–170.PubMedCrossRefGoogle Scholar
  110. 110.
    Doerfler W. Patterns of DNA methylation-Evolutionary vestiges of foreign DNA inactivation as a host defence mechanism. Biol Chem Hoppe-Seyler 1991; 372: 557–564.PubMedCrossRefGoogle Scholar
  111. 111.
    Antequera F, Macleod D, Bird A. Specific protection of methylated CpGs in mammalian nuclei. Cell 1989; 58: 509–517.PubMedCrossRefGoogle Scholar
  112. 112.
    Rösl F, Arab A, Klevenz B, zur Hausen H. The effect of DNA methylation on gene expression of human papillomaviruses. J Gen Virol 1993; 74: 791–801.PubMedCrossRefGoogle Scholar
  113. 113.
    Thain A, Jenkins O, Clarke AR et al. CpG methylation directly inhibits binding of the human papillomavirus type E2 protein to specific DNA sequences. J Virol 1996; 70: 7233–7235.PubMedGoogle Scholar
  114. 114.
    Boyes J, Bird A. DNA methylation inhibits transcription indirectly via a methyl-CpG binding protein. Cell 1991; 64: 1123–1134.PubMedCrossRefGoogle Scholar
  115. 115.
    Levine A, Cantoni G, Razin A. Inhibition of promoter activity by methylation: possible involvement of protein mediators. Proc Natl Acad Sci USA 1991; 88: 6515–6518.PubMedCrossRefGoogle Scholar
  116. 116.
    Meehan RR, Lewis JD, McKay S et al. Identification of a mammalian protein that binds specifically to DNA containing methylated CpGs. Cell 1989; 58: 499–507.PubMedCrossRefGoogle Scholar
  117. 117.
    Antequera F, Boyes J, Bird AP. High levels of de novo methylation and altered chromatin structure at CpG islands in cell lines. Cell 1990; 72: 503–514.CrossRefGoogle Scholar
  118. 118.
    Razin A, Cedar H. DNA methylation and gene expression. Microbiol Reviews 1991; 55: 451–458.Google Scholar
  119. 119.
    Bednarik DP, Cook JA, Pitha PM. Inactivation of the HIV LTR by DNA CpG methylation: evidence for a role in latency. EMBO J 1990; 9: 1157–1164.PubMedGoogle Scholar
  120. 120.
    Peng X, Lang CM, Kreider JW. Methylation of cottontail rabbit papillomavirus DNA and tissue-specific expression in transgenic rabbits. Virus Res 1995; 35: 101–108.PubMedCrossRefGoogle Scholar
  121. 121.
    Christy BA, Scangos GA. In vitro methylation of bovine papillomavirus alters its ability to transform mouse cells. Mol Cell Biol 1986; 6: 2910–2915.PubMedGoogle Scholar
  122. 122.
    Counts JL, Goodman JI. Alterations in DNA methylation may play a variety of roles in carcinogenesis. Cell 1995; 83: 13–15.PubMedCrossRefGoogle Scholar
  123. 123.
    Butterworth CE. Effect of folate on cervical cancer. Synergism among risk factors. Ann N Y Acad Sci 1992; 669: 293–299.PubMedCrossRefGoogle Scholar
  124. 124.
    Cravo M, Fidalgo P, Pereira AD et al. DNA methylation as an intermediate biomarker in colorectal cancer: modulation by folic acid supplementation. Eur J Cancer Prey 1994; 3: 473–479.CrossRefGoogle Scholar
  125. 125.
    Durst M, Petrussevska RT, Boukamp P et al. Molecular and cytogenetic analysis of immortalized human primary keratinocytes obtained after transfection with human papillomavirus 16 DNA. Oncogene 1987; 1: 251–256.PubMedGoogle Scholar
  126. 126.
    Pirisi L, Batova A, Jenkins GR et al. Increased sensitivity of human keratinocytes immortalized by human papillomavirus type 16 to growth control by retinoids. Cancer Res 1992; 52: 187–193.PubMedGoogle Scholar
  127. 127.
    Kaur P, McDougall JK. HPV18 immortalization of human keratinocytes. Virology 1989; 173: 302–310.PubMedCrossRefGoogle Scholar
  128. 128.
    Durst M, Seagon S, Wanschura S et al. Malignant progression of an HPV16 immortalized human keratinocyte cell line (HPK la) in vitro. Cancer Genet Cytogenet 1995; 85: 105–112.PubMedCrossRefGoogle Scholar
  129. 129.
    Hurlin PJ, Kaur P, Smith PP et al. Progression of human papillomavirus type 18-immortalized human keratinocytes to a malignant phenotype. Proc Natl Acad Sci USA 1991; 88: 570–574.PubMedCrossRefGoogle Scholar
  130. 130.
    DiPaolo JA, Woodworth CD, Popescu NC et al. Induction of human cervical cell carcinoma by sequential transfection with human papillomavirus 16 DNA and viral Harvey ras. Oncogene 1989; 4: 395–399.PubMedGoogle Scholar
  131. 131.
    Durst M, Gallahan D, Jay G et al. Glucocorticoid-enhanced neoplastic transformation of human keratinocytes by human papillomavirus type 16 and an activated ras oncogene. Virology 1989; 173: 767–771.PubMedCrossRefGoogle Scholar
  132. 132.
    Rhim JS, Webber MM, Bello D et al. Stepwise immortalization and transformation of adult human prostate epithelial cells by a combination of HPV18 and v-Ki-ras. Proc Natl Acad Sci USA 1994; 91: 11874–11878.PubMedCrossRefGoogle Scholar
  133. 133.
    de Villiers E-M, Wagner D, Schneider A et al. Human papillomavirus DNA in women without and with cytological abnormalities: results of a five-year follow-up study. Gynecol Oncol 1992; 44: 33–39.PubMedCrossRefGoogle Scholar
  134. 134.
    zur Hausen H. Intracellular surveillance of persisting viral infections: human genital cancer results from deficient cellular control of papillomavirus gene expression. Lancet 1986;ii:489–491.Google Scholar
  135. 135.
    zur Hausen H. Disrupted dichotomous intracellular control of human papillomavirus infection in cancer of the cervix. Lancet 1994; 343: 955–957.PubMedCrossRefGoogle Scholar
  136. 136.
    Stewart N, Bacchetti S. Expression of SV40 large T antigen, but not small t antigen, is required for the induction of chromosomal aberrations in transformed human cells. Virology 1991; 180: 49–57.PubMedCrossRefGoogle Scholar
  137. 137.
    Hashida T, Yasumoto S. Induction of chromosomal abnormalities in mouse and human epidermal keratinocytes by human papillomavirus type 16 E7 oncogene. J Gen Virol 1991; 72: 1569–1577.PubMedCrossRefGoogle Scholar
  138. 138.
    Stanbridge E. Genetic analysis of tumorigenicity in human cell hybrids. Cancer Surveys 1984; 3: 335–350.Google Scholar
  139. 139.
    Srivatsan ES, Benedict WF, Stanbridge EJ. Implication of chromosome 11 in the suppression of neoplastic expression in human cell hybrids. Cancer Res 1986; 46: 6174–6179.PubMedGoogle Scholar
  140. 140.
    Srivatsan ES, Misra BC, Venugopalan M et al. Loss of heterozygosity for alleles on chromosome 11 in cervical carcinoma. Am J Hum Genet 1991; 49: 868–877.PubMedGoogle Scholar
  141. 141.
    Saxon PJ, Srivatsan ES, Stanbridge EJ. Introduction of human chromosome 11 via microcell transfer controls tumorigenic expression of HeLa cells. EMBO J 1986; 5: 3461–3466.PubMedGoogle Scholar
  142. 142.
    Koi M, Morita H, Yamada H et al. Normal human chromosome 11 suppresses tumorigenicity of human cervical tumor cell line SiHa. Mol Carcinogenesis 1989; 2: 12–21.CrossRefGoogle Scholar
  143. 143.
    Smits PHM, Smits HL, Jebbink MF et al. The short arm of chromosome 11 likely is involved in the regulation of the human papillomavirus type 16 early enhancer-promoter and in the suppression of the transforming activity of the viral DNA. Virology 1990; 176: 158–165.PubMedCrossRefGoogle Scholar
  144. 144.
    Smits PHM, Smits HL, Minnaar RP et al. The 55 kDa regulatory subunit of protein phosphatase 2A plays a role in the activation of the HPV16 long control region in human cells with a deletion in the short arm of chromosone 11. EMBO J 1992; 11: 4601–4608.PubMedGoogle Scholar
  145. 145.
    Jones PA. DNA methylation errors and cancer. Cancer Res 1996; 56: 2463–2467.PubMedGoogle Scholar
  146. 146.
    Rösl F, Dürst M, zur Hausen H. Selective suppression of human papillomavirus transcription in nontumorigenic cells by 5-azacytidine. EMBO J 1988; 7: 1321–1328.PubMedGoogle Scholar
  147. 147.
    Little M, Wainwright B. Methylation and p16: Suppressing the suppressor. Nature Med 1995; 1: 633–634.PubMedCrossRefGoogle Scholar
  148. 148.
    Loughran O, Malliri A, Owens D et al. Association of CDKN2A/ p 16INK4A with human head and neck keratinocyte replicative senescence: relationship of dysfunction to immortality and neoplasia. Oncogene 1996; 13: 561–568.PubMedGoogle Scholar
  149. 149.
    von Knebel Doeberitz M, Oltersdorf T, Schwarz E et al. Correlation of modified human papillomavirus early gene expression with altered growth properties in C4–1 cervical carcinoma cells. Cancer Res 1988; 48: 3780–3786.Google Scholar
  150. 150.
    von Knebel Doeberitz M, Rittmüller C, zur Hausen H et al. Inhibition of tumorigenicity of cervical cancer cells in nude mice by HPV E6–E7 anti-sense RNA. Int J Cancer 1992; 51: 831–834.CrossRefGoogle Scholar
  151. 151.
    Crook CP, Morgenstern JP, Crawford L et al. Continued expression of HPV16 E7 protein is required for maintenance of the transformed phenotype of cells cotransformed by HPV16 plus EJ-ras. EMBO J 1989; 8: 513–519.PubMedGoogle Scholar
  152. 152.
    Rösl F, Achtstätter T, Bauknecht T et al. Extinction of the HPV18 upstream regulatory region in cervical carcinoma cells after fusion with nontumorigenic human keratinocytes under nonselective condition. EMBO J 1991; 10: 1337–1345.PubMedGoogle Scholar
  153. 153.
    Chen T-M, Pecoraro G, Defendi V. Genetic analysis of in vitro progression of human papillomavirus-transfected human cervical cells. Cancer Res 1993; 53: 1167–1171.PubMedGoogle Scholar
  154. 154.
    Seagon S, Durst M. Genetic analysis of an in vitro model system for human papillomavirus type 16-associated tumorigenesis. Cancer Res 1994; 54: 5593–5598.PubMedGoogle Scholar
  155. 155.
    Durst M, Bosch FX, Glitz D et al. Inverse relationship between HPV16 early gene expression and cell differentiation in nude mouse epithelial cysts and tumors induced by HPV positive human cell lines. J Virol 1991; 65: 796–804.PubMedGoogle Scholar
  156. 156.
    Bosch FX, Schwarz E, Boukamp P et al. Suppression in vivo of human papillomavirus type 18 E6–E7 gene expression in nontumorigenic HeLa-fibroblast hybrid cells. J Virol 1990; 64: 4743–4754.PubMedGoogle Scholar
  157. 157.
    zur Hausen H. Human papillomaviruses in the pathogenesis of anogenital cancer. Virology 1991; 184: 9–13.PubMedCrossRefGoogle Scholar
  158. 158.
    zur Hausen H, Rösl F. Pathogenesis of cancer of the cervix. Cold Spring Harbor Symposia on Quantitative Biology, 1994 Vol. LIX, pp. 623–628. Cold Spring Harbor Laboratory Press.Google Scholar
  159. 159.
    Khan MA, Jenkins GR, Tolleson, WH et al. Retinoic acid inhibition of human papillomavirus type 16-mediated transformation of human keratinocytes. Cancer Res 1993; 53: 905–909.PubMedGoogle Scholar
  160. 160.
    Suzuki T, Okuno H, Yoshida T et al. Difference in transcriptional regulatory function between c-Fos and Fra-2. Nucl Acids Res 1991; 19: 5537–5542.PubMedCrossRefGoogle Scholar
  161. 161.
    Yoshioka K, Deng T, Cavigelli M et al. Antitumor promotion by phenolic antioxidants: inhibition of AP-1 activity through induction of fra expression. Proc Natl Acad Sci USA. 1995; 92: 4972–4976.PubMedCrossRefGoogle Scholar
  162. 162.
    Sinke RJ, Tanigami A, Nakamura Y et al. Reverse mapping of the gene encoding the human fos-related antigen-1 (fra-1) within chromosome band 11q13. Genomics 1993; 18: 165.PubMedCrossRefGoogle Scholar
  163. 163.
    Jesudasan RA, Rahman RA. Chandrashekharappa S et al. Deletion and translocation of chromosome 11813 sequences in cervical carcinoma cell lines. Am J Hum Genet 1995; 56:705–715.Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • Frank Rösl
  • Elisabeth Schwarz

There are no affiliations available

Personalised recommendations