Skip to main content
SpringerLink
Log in

Molecular Pathogenesis of Cancer of the Cervix and Its Causation by Specific Human Papillomavirus Types

  • Chapter
Human Pathogenic Papillomaviruses

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 186))

Abstract

Less than 10 years after publication of the hypothesis of a papillomavirus etiology of cancer of the cervix (zur Hausen 1975, 1976, 1977), the DNAs of the first cervical cancer-associated human papillomavirus (HPV) types were cloned and characterized. These DNAs are regularly and frequently found in biopsies obtained from cervical cancer patients throughout the world (Dürst et al. 1983; Boshart et al. 1984).

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

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Arbeit JM, Münger K, Howley PM, Hanahan D. Neuroepithelial carcinomas in mice transgenic with human papillomavirus type 16 E6/E7 ORF’s. Am J Pathol (in press).

    Google Scholar 

  • Atkin NB, Baker MC (1984) Non-random chromosome changes in carcinoma of the cervix uteri. I. Nine near-diploid tumors. Cancer Genet Cytogenet 7:2209–2221.

    Google Scholar 

  • Atkin NB, Baker MC (1988) Deficiency of all or part of chromosome 11 in several types of cancer: significance of a reduction in the number of normal chromosomes 11. Cytogenet Cell Genet 47:106–107.

    Article  PubMed  CAS  Google Scholar 

  • Auvinen E, Kujari H, Arstila P, Hukkanen V. Expression of α2 and E7 genes of the human papillomavirus type 16 in female genital dysplasias. Am J Pathol (in press).

    Google Scholar 

  • Band V, Zaychowski D, Kulesa V, Sager R (1990) Human papillomavirus DNAs immortalize normal human mammary epithelial cells and reduce their growth factor requirements. Proc Nat Acad Sci USA 87:463–467.

    Article  PubMed  CAS  Google Scholar 

  • Band V, Dalai S, Delmolino L, Androphy EJ (1993) Enhanced degradation of p53 protein in HPV-6 and BPV-1 immortalized human mammary epithelial cells. EMBO J 12:1847–1852.

    PubMed  CAS  Google Scholar 

  • Barbosa MS, Edmonds C, Fisher C, Schiller JT, Lowy DR, Vousden KH (1990) The region of the HPV E7 oncoprotein homologous to adenovirus E1A and SV40 large T antigen contains separate domains for Rb binding and casein kinase II phosphorylation. EMBO J 9:153–160.

    PubMed  CAS  Google Scholar 

  • Bartsch D, Boye B, Baust C, zur Hausen H, Schwarz E (1992) Retinoic acid-mediated repression of human papillomavirus 18 transcription and different ligand regulation of the retinoic acid receptor β gene in non-tumorigenic and tumorigenic HeLa hybrid cells. EMBO J 11: 2283–2291.

    PubMed  CAS  Google Scholar 

  • Batova A, Danielpour D, Pirisi L, Creek KE (1992) Retinoic acid induces secretion of latent transforming growth factor beta 1 and beta 2 in normal and human papillomavirus type 16-immortalized human keratinocytes. Cell Growth Differ 3:763–772.

    PubMed  CAS  Google Scholar 

  • Bauknecht T, Angel P, Royer H-D, zur Hausen H (1992) Identification of a negative regulatory domain in the human papillomavirus type 18 promoter: interaction with the transcriptional repressor YY1. EMBO J 11:4607–4617.

    PubMed  CAS  Google Scholar 

  • Bosch F, Schwarz E, Boukamp P, Fusenig NE, Bartsch D, zur Hausen H (1990) Suppression in vivo of human papillomavirus type 18 E6–E7 gene expression in nontumorigenic HeLa-fibroblast hybrid cells. J Virol 64:4743–4754.

    PubMed  CAS  Google Scholar 

  • Boshart M, zur Hausen H (1986) Human papillomaviruses in Buschke-Löwenstein tumors: physical state of DNA and identification of a tandem duplication in the non-coding region of a human papillomavirus 6 subtype. J Virol 58:963–966.

    PubMed  CAS  Google Scholar 

  • Boshart M, Gissmann L, Ikenberg H, Kleinheinz A, Scheurlen W, zur Hausen H (1984) A new type of papillomavirus DNA, its presence in genital cancer biopsies and in cell lines derived from cervical cancer. EMBO J 3:1151–1157.

    PubMed  CAS  Google Scholar 

  • Braun L, Dürst M, Mikumo R, Guipposo P (1990) Differential response of nontumorigenic and tumorigenic human papillomavirus type 16-positive epithelial cells to transforming growth factor β. Cancer Res 50:7324–7332.

    PubMed  CAS  Google Scholar 

  • Burnett S, Ström AC, Jareborg N, Alderborn A, Dillner J, Moreno-Lopez J, Pettersson U, Kiessling N (1990) Induction of E2 gene expression and early region transcription by cell growth arrest: correlation with viral DNA amplification and evidence for differential promoter induction. J Virol 64:5529–5541.

    PubMed  CAS  Google Scholar 

  • Chan WK, Klock G, Bernard HU (1989) Progesterone and glucocorticoid control elements occur in the long control regions of several human papillomaviruses involved in anogenital neoplasia. J Virol 63:3261–3269.

    PubMed  CAS  Google Scholar 

  • Chan WK, Chong T, Bernard HU, Klock G (1990) Transcription of the transforming genes of the oncogenic human papillomavirus-16 is stimulated by tumor promoters through AP-1 binding sites. Nucleic Acid Res 18:763–769.

    Article  PubMed  CAS  Google Scholar 

  • Chellappan SP, Hieben S, Mudryj M, Horowitz JM, Nevins JR (1991) The E2F transcription factor is a cellular target of the RB protein. Cell 65, 1053–1061.

    Article  PubMed  CAS  Google Scholar 

  • Chen T-M, Pecoraro G, Defendi V (1993) Genetic analysis of in vitro progression of human papillomavirus-transfected human cervical cells. Cancer Res 53:1167–1171.

    PubMed  CAS  Google Scholar 

  • Chittenden T, Livingston DM, Kaelin WG Jr (1991) The T/E1 A-binding domain of the retinoblastoma product can interact selectively with a sequence-specific DNA binding protein. Cell 65:1073–1082.

    Article  PubMed  CAS  Google Scholar 

  • Cid A, Auewarakul P, Garcia-Carranca A, Ovseiovich R, Gaissert H, Gissmann L (1993) Cell-type specific activity of the human papillomavirus (HPV) type 18 upstream regulatory region in transgenic mice and its modulation by TPA and glucocorticoids. J Virol 67:6742–6752.

    PubMed  CAS  Google Scholar 

  • Cripe TP, Alderborn A, Anderson RD, Pakkinen S, Bergman T, Haugen H, Petterson V, Turek LP (1990) Transcriptional activation of the human papillomavirus-16 P97 promoter by an 88 nucleotide enhancer containing distinct cell-dependent and AP-1 responsive modules. New Biol 2:450–463.

    PubMed  CAS  Google Scholar 

  • Crook T, Vousden KH (1992) Properties of p53 mutations detected in primary and secondary cervical cancers suggest mechanisms of metastasis and involvement of environmental carcinogens. EMBO J 11:3935–3940.

    PubMed  CAS  Google Scholar 

  • Crook T, Morgenstern JP, Crawford L, Banks L (1989) Continued expression of HPV16 E7 protein is required for maintenance of the transformed phenotype of cells co-transformed by HPV 16 plus EJ-ras. EMBO J 8:513–519.

    PubMed  CAS  Google Scholar 

  • Crum CP, Nagai N, Milao M, Levine RU, Silverstein SJ (1985) Histological and molecular analysis of early neoplasia. J Cell Biochem [Suppl] 9c:70.

    Google Scholar 

  • Cullen AP, Reid R, Campion M, Lorincz AT (1991) Analysis of the physical state of different human papillomavirus DNA’s in intraepithelial and invasive cervical neoplasms. J Virol 65:606–612.

    PubMed  CAS  Google Scholar 

  • Debiec-Rychter M, Zukowski K, Wang CY, Wen W-N (1991) Chromosomal characterizations of human nasal and nasopharyngeal cells immortalized by human papillomavirus type 16 DNA. Cancer Genet Cytogenet 52:51–61.

    Article  PubMed  CAS  Google Scholar 

  • Defoe-Jones D, Vuocolo GA, Haskell KM, Hanobik MG, Kiefer DM, McAvoy EM, Ivey-Hoyle M, Brandsma JL, Oliff A, Jones RE (1993) Papillomavirus E7 protein binding to the retinoblastoma protein is not required for viral induction of warts. J Virol 67:716–725.

    Google Scholar 

  • Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery CA, Butel JS, Bradley A (1992) Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 356:215–221.

    Article  PubMed  CAS  Google Scholar 

  • Drews RE, Chan VT-W, Schnipper LE (1992) Oncogenes result in genomic alterations that activate a transcriptionally silent dominantly selectable reporter gene (neo). Mol Cell Biol 12:198–206.

    PubMed  CAS  Google Scholar 

  • Dürst M, Gissmann L, Ikenberg H, zur Hausen H (1983) A new papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proc Natl Acad Sci USA 80:3812–3815.

    Article  PubMed  Google Scholar 

  • Dürst M, Kleinheinz A, Hotz M, Gissmann L (1985) The physical state of human papillomavirus type 16 DNA in benign and malignant genital tumors. J Gen Virol 66:1515–1522.

    Article  PubMed  Google Scholar 

  • Dürst M, Dzarlieva-Petrusevska RT, Boukamp P, Fusenig NE, Gissmann L (1987) Molecular and cytogenetic analysis of immortalized human primary keratinocytes obtained after transfection with human papillomavirus type 16 DNA. Oncogene 1:251–256.

    PubMed  Google Scholar 

  • Dürst M, Bosch F, Glitz D, Schneider A, zur Hausen H (1991) Inverse relationship between HPV 16 early gene expression and cell differentiation in nude mice epithelial cysts and tumors induced by HPV positive human cell lines. J Virol 65:796–804.

    PubMed  Google Scholar 

  • Dürst M, Glitz D, Schneider A, zur Hausen H (1992) Human papillomavirusestype 16 (HPV16) gene expression and DNA replication in cervical neoplasia: analysis by in situ hybridization. Virology 189:132–140.

    Article  PubMed  Google Scholar 

  • Dyson N, Howley PM, Münger K, Harlow E (1989) The human papillomavirus 16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science 243:934–937.

    Article  PubMed  CAS  Google Scholar 

  • Evans AS (1976) Epidemiological concepts and methods. In: Evans AS (ed) Viral infections of humans, epidemiology and control. Wiley, London, pp 1–32.

    Chapter  Google Scholar 

  • Fu Y-S, Braun L, Shah KV, Lawrence WP, Robboy SJ (1983) Histologie, nuclear DNA and human papillomavirus studies of cervical condylomas. Cancer 52:1705–1711.

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Carranca A, Thierry F, Yaniv M (1988) Interplay of viral and cellular proteins along the long control region of human papillomavirus 18. J Virol 63:4321–4330.

    Google Scholar 

  • Gebert JF, Moghal N, Frangioni JV, Sugarbaker DJ, Neel BG (1991) High frequency of retinoic acid receptor β abnormalities in human lung cancer. Oncogene 6:1859–1868.

    PubMed  CAS  Google Scholar 

  • Gloss B, Bernard HU (1990) The E6/E7 promoter of human papillomavirus type 16 is activated in the absence of E2 proteins by a sequence-aberrant SP I distal element. J Virol 64:5577–5584.

    PubMed  CAS  Google Scholar 

  • Gloss B, Bernard HU, Seedorf K, Klock G (1987) The upstream regulatory region of human papillomavirus-16 contains an E2 protein-independent enhancer which is specific for cervical carcinoma cells and regulated by glucocorticoid hormones. EMBO J 6:3735–3743.

    PubMed  CAS  Google Scholar 

  • Gloss B, Chong T, Bernard HU (1989) Numerous nuclear factors bind the long control region of human papillomavirus type 16: a subset of 6 out of 23 DNase l-protected segments coincides with the location of the cell-type-specific enhancer. J Virol 63:1142–1152.

    PubMed  CAS  Google Scholar 

  • Griep AE, Herber R, Jeon S, Lohse JK, Dubielzig RR, Lambert P (1993) Tumorigenicity by HPV 16 E6 and E7 in transgenic mice correlates with alterations in epithelial cell growth and differentiation. J Virol 67:1373–1384.

    PubMed  CAS  Google Scholar 

  • Gross L (1983) Oncogenic viruses, 3rd edn. Pergamon, Oxford.

    Google Scholar 

  • Halbert CL, Demers GW, Galloway DA (1991) The E7 gene of human papillomavirus type 16 is sufficient for immortalization of human keratinocytes. J Virol 65:473–478.

    PubMed  CAS  Google Scholar 

  • Han R, Breitburd F, Marche PN, Orth G (1992) Linkage of regression and malignant conversion of rabbit viral papillomas to MHC class II genes. Nature 356:66–68.

    Article  PubMed  CAS  Google Scholar 

  • Hartwell L (1992) Defects in a cell cycle check point may be responsible for the genomic instability of cancer cells. Cell 71:543–546.

    Article  PubMed  CAS  Google Scholar 

  • Hashida T, Yasumoto S (1991) Induction of chromosome abnormalities in mouse and human epidermal keratinocytes by the human papillomavirus type 16 E7 oncogene. J Gen Virol 72:1569–1577.

    Article  PubMed  CAS  Google Scholar 

  • Haskell KM, Vuocolo GA, Defoe-Jones D, Jones RE, Ivey-Hoyle M (1993) Comparison of the binding of the human papillomavirus type 16 and cottontail rabbit papillomavirus E7 proteins to retinoblastoma gene product. J Gen Virol 74:115–119.

    Article  PubMed  CAS  Google Scholar 

  • Hawley-Nelson P, Vousden KH, Hubbert NL, Lowy DR, Schiller JT (1989) HPV 16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes. EMBO J. 8:3905–3910.

    PubMed  CAS  Google Scholar 

  • Heck DV, Yee CL, Howley PM, Münger K (1992) Efficiency of binding the retinoblastoma protein correlates with the transforming capacity of the E7 oncoproteins of the human papillomaviruses. Proc Natl Acad Sci USA 89:4442–4446.

    Article  PubMed  CAS  Google Scholar 

  • Heiland A, Borresen AL, Kaern J, Ronningen KS, Thorsby E (1992) HLA antigens and cervical cancer. Nature 356:23.

    Article  Google Scholar 

  • Hoppe-Seyler F, Butz K (1992) Activation of human papillomavirus type 18 E6–E7 oncogene expression by transcription factor Sp1. Nucleic Acid Res 20:6701–6706.

    Article  PubMed  CAS  Google Scholar 

  • Hoppe-Seyler F, Butz K, zur Hausen H (1991) Repression of the human papillomavirus type 18 enhancer by the cellular transcription factor Oct-1. J Virol 65:5613–5618.

    PubMed  CAS  Google Scholar 

  • Houle B, Rochette-Egly C, Bradley WEC (1993) Tumor-suppressive effect of the retinoic acid receptor β in human epidermoid lung cancer cells. Proc Natl Acad Sci USA 90:985–989.

    Article  PubMed  CAS  Google Scholar 

  • Howley PM (1991) Role of human papillomaviruses in human cancer. Cancer Res 51:5019–5022.

    Google Scholar 

  • Hubbert S, Schiller JT, Lowy DR, Androphy EJ (1988) Bovine papillomavirus transformed cells contain multiple E2 proteins. Proc Natl Acad Sci USA 85:5864–5868.

    Article  PubMed  CAS  Google Scholar 

  • Hubbert NL, Sedman SA, Schiller JT (1992) Human papillomavirus type 16 E6 increases the degradation rate of p53 in human keratinocytes. J Virol 66:6237–6241.

    PubMed  CAS  Google Scholar 

  • Hudson JB, Bedell ML, McCance DJ, Laimins LA (1990) Immortalization and altered differentiation of human keratinocytes in vitro by the E6 and E7 open reading frames of human papillomavirus type 18. J Virol 64:519–529.

    PubMed  CAS  Google Scholar 

  • Hurlin PJ, Kaur P, Smith P, Perez-Reyes N, Blanton RA, McDougall JK (1991) Progression of human papillomavirus type 18 immortalized human keratinocytes to a malignant phenotype. Proc Natl Acad Sci USA 88:570–574.

    Article  PubMed  CAS  Google Scholar 

  • Iftner T, Oft M, Böhm S, Wolczynski SP, Pfister H (1992) Transcription of the E6 and E7 genes of human papillomavirus type 6 in anogenital condylomata is restricted to undifferentiated cell layers of the epithelium. J Virol 66:4639–4646.

    PubMed  CAS  Google Scholar 

  • Ishiji T, Lace MJ, Parkhinen S, Anderson RD, Haugen TH, Cripe TP, Xiao J-H, Davidson I, Chambon P, Turek LP (1992) Transcriptional enhancer factor (TEF)-1 and its cell-specific co-activator activate human papillomavirus-16 E6 and E7 oncogene transcription in keratinocytes and cervical carcinoma cells. EMBO J 11:2271–2281.

    PubMed  CAS  Google Scholar 

  • Jagella HP, Stegner HE (1974) Zur Dignität der Condylomata acuminata. Klinische, histopathologische und cytophotometrische Befunde. Arch Gynaekol 216:119–132.

    Article  CAS  Google Scholar 

  • Jewers RJ, Hildebrandt P, Ludlow JW, Kell B, McCance DJ (1992) Regions of human papillomavirus type 16 E7 oncoprotein required for immortalization of human keratinocytes. J Virol 66:1329–1335.

    PubMed  CAS  Google Scholar 

  • Kaebling M, Klinger HP (1986) Suppression of tumorigenicity in somatic cell hybrids. III. Co-segregation of human chromosome 11 of a normal cell and suppression of tumorigenicity in intraspecies hybrids of normal diploid-malignant cells. Cytogenet Cell Genet 41:65–70.

    Article  Google Scholar 

  • Kaelin WG, Pallas DC, DeCaprio JA, Kaye FJ, Livingston DM (1991) Identification of cellular proteins that can interact specifically with the T/E1 A-binding region of the retinoblastoma gene product. Cell 64, 521–532.

    Article  PubMed  CAS  Google Scholar 

  • Karlen S, Beard P (1993) Identification and characterization of novel promoters in the genome of human papillomavirus type 18. J Virol 67:4296–4306.

    PubMed  CAS  Google Scholar 

  • Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW (1991) Participation of p53 protein in the cellular response to DNA damage. Cancer Res. 51:6304–6311.

    PubMed  CAS  Google Scholar 

  • Kessis TD, Slebos RJ, Nelson WG, Kastan MB, Plunkett BS, Hau SM, Lorincz AT, Hedrick L, Cho KR (1993) Human papillomavirus 16 E6 expression disrupts the p53-mediated cellular response to DNA damage. Proc Natl Acad Sci USA 90:3988–3992.

    Article  PubMed  CAS  Google Scholar 

  • Koch R (1891) Ãœber bakteriologische Forschung. Verhandlungen des 10 Internationalen Medizinischen Congress, Berlin, Voll, p35.

    Google Scholar 

  • Koi M, Morita H, Yamada H, Saboh H, Barrett JC, Oshimura H (1989) Normal human chromosome 11 suppresses tumorigenicity of human cervical tumor cell line SiHa. Mol Carcinog 2:12–21.

    Article  PubMed  CAS  Google Scholar 

  • Kondoh G, Murata Y, Aozasa K, Yutsudo M, Hakura A (1991) Very high incidence of germ cell tumorigenesis (seminomagenesis) in human papillomavirus type 16 transgenic mice. J Virol 65:3335–3339.

    PubMed  CAS  Google Scholar 

  • Kyo S, Inoue M, Nishio Y, Nakanishi K, Akira S, Inoue H, Yutsudo M, Tanizawa O, Hakura A (1993) NF-IL 6 represses early gene expression of human papillomavirus type 16 through binding to the noncoding region. J Virol 67:1058–1066.

    PubMed  CAS  Google Scholar 

  • Lambert PF, Spalholz BA, Howley PM (1987) A transcriptional repressor encoded by BPV-1 shares common carboxy-terminal domain with the E2 transactivator. Cell 50:69–78.

    Article  PubMed  CAS  Google Scholar 

  • Lane DP (1992) p53, guardian of the genome. Nature 358:15–16.

    Article  PubMed  CAS  Google Scholar 

  • Lechner MS, Mack DH, Finicle AB, Crook T, Vousden KH, Laimins LA (1992) Human papillomavirus E6 proteins bind p53 in vivo and abrogate p53-mediated repression of transcription. EMBO J 11:3045–3052.

    PubMed  CAS  Google Scholar 

  • Lehn H, Villa LL, Marziona F, Hilgarth M, Hillemanns HG, Sauer G (1988) Physical state and biological activity of human papillomavirus genomes in precancerous lesions of the female genital tract. J Gen Virol 69:187–196.

    Article  PubMed  Google Scholar 

  • Leid M, Kastner P, Chambon P (1992) Multiplicity generates diversity in the retinoic acid signalling pathways. TIBS 17:427–433.

    PubMed  CAS  Google Scholar 

  • Mack DH, Laimins LA (1991) A keratinocyte-specific transcription factor, KRE-1, interacts with AP-1 to activate expression of human papillomavirus type 18 in squamous epithelial cells. Proc Natl Acad Sci USA 88:9102–9106.

    Article  PubMed  CAS  Google Scholar 

  • Malejczyk J, Malejczyk M, Urbanski A, Köck A, Jablonska S, Orth G, Luger T (1991) Constitutive release of IL 6 by human papillomavirus type 16 (HPV 16)-harboring keratinocytes: a mechanism augmenting the NK-cell-mediated lysis of HPV-bearing neoplastic cells. Cell Immunol 136:155–164.

    Article  PubMed  CAS  Google Scholar 

  • Malejczyk J, Malejczyk M, Köck A, Urbanski A, Majewski S, Hunzelmann N, Jablonska S, Orth G, Luger TA (1992) Autocrine growth limitation of human papillomavirus type 16— harboring keratinocytes by constitutively released tumor necrosis factor-α. J Immunol 149:2702–2708.

    PubMed  CAS  Google Scholar 

  • Matsukura T, Koi S, Sugase M (1989) Both episomal and integrated forms of human papillomavirus type 16 are involved in invasive cervical cancers. Virology 172:63–72.

    Article  PubMed  CAS  Google Scholar 

  • McCance DJ, Kopan R, Fuchs E, Laimins LA (1988) Human papillomavirus type 16 alters human epithelial cell differentiation in vitro. Proc Natl Acad Sci USA 85:7169–7173.

    Article  PubMed  CAS  Google Scholar 

  • Münger K, Phelps WC, Bubb V, Howley PM, Schlegel R (1989) The E6 and E7 genes of human papillomavirus type 16 are necessary and sufficient for transformation of primary human keratinocytes. J Virol 63:4417–4421.

    PubMed  Google Scholar 

  • Nevins JR (1992a) E2F: a link between Rb tumor suppressor protein and viral oncoproteins. Science 258, 424–429.

    Article  PubMed  CAS  Google Scholar 

  • Nevins JR (1992b) Transcriptional regulation. A closer look at E2F. Nature 358,375–376.

    Article  PubMed  CAS  Google Scholar 

  • Offord EA, Beard P (1990) 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 64:4792–4798.

    PubMed  CAS  Google Scholar 

  • Pagano M, Dürst M, Joswig S, Draetta G, Jansen-Dürr P (1992) Binding of human E2F transcription factor to the retinoblastoma protein but not cyclin A is abolished in HPV 16-immortalized cells. Oncogene 7:1681–1687.

    PubMed  CAS  Google Scholar 

  • Park N-H, Min B-M, Li S-L, Huang MZ, Cherick HM, Doninger J (1991) Immortalization of normal human oral keratinocytes with type 16 human papillomavirus. Carcinogenesis 12:1627–1631.

    Article  PubMed  CAS  Google Scholar 

  • Pater MM, Hughes GA, Hyslop DE, Nakshatri H, Pater A (1988) Glucocorticoid-dependent oncogenic transformation by type 16 and not type 11 human papillomavirus DNA. Nature 335:832–835.

    Article  PubMed  CAS  Google Scholar 

  • Pecoraro G, Lee M, Morgan D, Defendi V (1991) Evolution of in vitro transformation and tumorigenesis of HPV 16 and HPV 18 immortalized primary cervical epithelial cells. Am J Pathol 138:1–8.

    PubMed  CAS  Google Scholar 

  • Peng X, Olson RO, Christian CB, Lang CM, Kreider JW (1993) Papillomas and carcinomas in transgenic rabbits carrying EJ-ras and cottontail rabbit papillomavirus DNA. J Virol 67:1698–1701.

    PubMed  CAS  Google Scholar 

  • Phelps WC, Baghi S, Barnes JA, Raychaudhuri P, Kraus V, Münger K, Howley PM, Nevius JR (1991) Analysis of transactivation by human papillomavirus type 16 E7 and adenovirus 12S E1A suggest a common mechanism J Virol 65:6922–8930.

    PubMed  CAS  Google Scholar 

  • Phelps WC, Münger K, Yee CL, Barnes JA, Howley PM (1992) Structure-function analysis of the human papillomavirus type 16 E7 oncoprotein. J Virol 66:2418–2427.

    PubMed  CAS  Google Scholar 

  • Pirisi L, Yasumoto S, Fellery M, Doninger JK, DiPaolo JA (1987) Transformation of human fibroblasts and keratinocytes with human papillomavirus type 16 DNA. J Virol 61:1061–1066.

    PubMed  CAS  Google Scholar 

  • Pirisi L, Batova A, Jenkins GR, Hodam, JR, Creek KE (1992) Increased sensitivity of human keratinocytes immortalized by human papillomavirus type 16 DNA to growth control by retinoids. Cancer Res 52:187–193.

    PubMed  CAS  Google Scholar 

  • Rösl F, Dürst M, zur Hausen H (1988) Selective suppression of human papillomavirus transcription in non-tumorigenic cells by 5-aza-cytidine. EMBO J 7:1321–1328.

    PubMed  Google Scholar 

  • Rösl F, Westphal E-M, zur Hausen H (1989) Chromatin structure and transcriptional regulation of human papillomavirus type 18 DNA in HeLa cells. Mol Carcinog 2:72–80.

    Article  PubMed  Google Scholar 

  • Rösl F, Achtstetter T, Hutter K-J, Bauknecht T, Futterman G, zur Hausen H (1991) Extinction of the HPV 18 upstream regulatory region in cervical carcinoma cells after fusion with nontumorigenic human keratinocytes under non-selective conditions. EMBO J 10:1337–1345.

    PubMed  Google Scholar 

  • Rösl F, Arab A, Klevenz B, zur Hausen H (1993) The effect of DNA methylation on gene regulation of human papillomaviruses. J Gen Virol 74:791–801.

    Article  PubMed  Google Scholar 

  • Rollins BJ, Sunday ME (1991) Suppression of tumor formation in vivo by expression of the JE gene in malignant cells. Mol Cell Biol 11:3125–3131.

    PubMed  CAS  Google Scholar 

  • Romanczuk H, Thierry F, Howley PM (1990) Mutational analysis of cis elements involved in E2 modulation of human papillomavirus type 16 P97 and 18 P105 promoters. J Virol 64:2849–2859.

    PubMed  CAS  Google Scholar 

  • Saxon PJ, Srivatsan ES, Stanbridge J (1986) Introduction of human chromosome 11 via microcell transfer controls tumorigenic expression in HeLa cells. EMBO J 5:3461–3466.

    PubMed  CAS  Google Scholar 

  • Scheffner M, Werness BA, Huibregtse JM, Levine JM, Howley PM (1990) The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63:1129–1136.

    Article  PubMed  CAS  Google Scholar 

  • Scheffner M, Münger K, Byrne JC, Howley PM (1991) The state of the p53 and retinoblastoma genes in human cervical carcinoma cell lines. Proc Natl Acad Sci USA 88:5523–5527.

    Article  PubMed  CAS  Google Scholar 

  • Schwarz E (1987) Transcription of papillomavirus genomes. In: Syrjänen K, Gissmann L, Koss LG (eds) Papillomaviruses and human disease. Springer, Berlin Heidelberg New York, pp 443–466.

    Chapter  Google Scholar 

  • Schwarz E, Freese UK, Gissmann L, Mayer W, Roggenbuck B, Stremlau A, zur Hausen H (1985) Structure and transcription of human papillomavirus sequences in cervical carcinoma cells. Nature 314:111–114.

    Article  PubMed  CAS  Google Scholar 

  • Searle PF, Thomas DP, Faulkner KB, Tinsley JM. Gastric carcinoma in transgenic mice expressing HPV 16 early region genes (submitted for publication).

    Google Scholar 

  • Sippola-Thiele M, Hanahan D, Howley PM (1989) Cell-heritable stages of tumor progression in transgenic mice harboring the bovine papillomavirus type 1 genome. Mol Cell Biol 9:925–934.

    PubMed  CAS  Google Scholar 

  • Sircar S, Horvath J, Roberge D, Diouri M, Weber JM (1992) Adenovirus transformation revertant resistant to retransformation by E1 but not by SV40-T and HPV 16-E7 oncogenes. Virology 191:187–192.

    Article  PubMed  CAS  Google Scholar 

  • Smith PP, Friedman CL, Bryand EM, McDougall JK (1992) Viral integration and fragile sites in human papillomavirus-immortalized human keratinocyte cell lines. Genes, Chrom Cancer 5:150–157.

    Article  CAS  Google Scholar 

  • Smits HL, Raadsheer E, Rood I, Mehendale S, Slater RM, van der Noordaa J, ter Schegget J (1988) Induction of anchorage-independent growth of human embryonic fibroblasts with a deletion in the short arm of chromosome 11 by human papillomavirus type 16 DNA. J Virol 62:4538–4543.

    PubMed  CAS  Google Scholar 

  • Smits PHM, deRonde A, Smits HL, Minaar RP, van der Noordaa J, ter Schegget J (1992a) Modulation of the human papillomavirus type 16 induced transformation and transcription by deletion of loci on the short arm of chromosome 11 can be mimicked by SV 40 small t. Virology 190:40–44.

    Article  PubMed  CAS  Google Scholar 

  • Smits PHM, Smits HL, Minnaar R, Hemmings BA, Mayer-Jaekel RE, Schuurman R, van der Noordaa J, ter Schegget J (1992b) The trans-activation of the HPV 16 long control region in human cells with a deletion in the short arm chromosome 11 is mediated by the 55kDa regulatory subunit of protein phosphatase 2A. EMBO J 11:4601–4606.

    PubMed  CAS  Google Scholar 

  • Smits PHM, Smits HL, Minnaar RP, ter Schegget J (1993) Regulation of human papillomavirus type 16 (H PV-16) transcription by loci on the short arm of chromosome 11 is mediated by the TATAAAA motif of the HPV 16 promoter. J Gen Virol 74:121–124.

    Article  PubMed  CAS  Google Scholar 

  • Smotkin D, Wettstein FO (1986) Transcription of human papillomavirus type 16 early genes in a cervical cancer and a cancer-derived cell line and identification of the E7 protein. Proc Natl Acad Sci USA 83:4680–4684.

    Article  PubMed  CAS  Google Scholar 

  • Spalholz BA, Yang Y-C, Howley PM (1985) Transactivation of bovine papillomavirus transcriptional regulatory element by the E2 gene product. Cell 42:183–191.

    Article  PubMed  CAS  Google Scholar 

  • Sreekantaiah C, de Braekeleer M, Haas O (1991) Cytogenetic findings in cervical carcinoma: a statistical approach. Cancer Genet Cytogenet 51:75–81.

    Article  Google Scholar 

  • Stoler MH, Rhodes CR, Whitbek A, Wolinsky SM, Chow LT, Broker TR (1992) Human papillomavirus type 16 and 18 gene expression in cervical neoplasias. Human Pathol 23:117–128.

    Article  CAS  Google Scholar 

  • Thierry F, Spyrou G, Yaniv M, Howley P (1992) Two AP-1 sites binding JunB are essential for human papillomavirus type 18 transcription in keratinocytes. J Virol 66:3740–3748.

    PubMed  CAS  Google Scholar 

  • von Knebel Doeberitz M, Oltersdorf T, Schwarz E, Gissmann L (1988) Correlation of modified human papillomavirus early gene expression with altered growth properties in C4-1 cervical carcinoma cells. Cancer Res. 48:3780–3786.

    Google Scholar 

  • von Knebel Doeberitz M, Bauknecht T, Bartsch D, zur Hausen H (1991) Influence of chromosomal integration on glucocorticoid regulated transcription of growth-stimulating E6–E7 genes in cervical carcinoma cells. Proc Natl Acad Sci USA 88:1411–1415.

    Article  Google Scholar 

  • von Knebel Doeberitz M, Rittmüller C, zur Hausen H, Dürst M (1992) Inhibition of tumorigenicity of C4-1 cervical cancer cells in nude mice by HPV 18 E6–E7 antisense RNA. Int J Cancer 51:831–834.

    Article  Google Scholar 

  • Wank R, Thomssen C (1991) High risk of squamous cell carcinoma of the cervix for women with HLA-DQw3. Nature 352:723–725.

    Article  PubMed  CAS  Google Scholar 

  • Wank R, Schendel DJ, Thomssen C (1992) HLA antigens and cervical carcinoma. Nature 356:22–23.

    Article  PubMed  CAS  Google Scholar 

  • Watanabe S, Kanda T, Yoshiike K (1989) Human papillomavirus type 16 transformation of primary human embryonic fibroblasts requires expression of open reading frames E6 and E7. J Virol 63:965–969.

    PubMed  CAS  Google Scholar 

  • Werness BA, Levine AJ, Howley PM (1990) Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science 248, 76–79.

    Article  PubMed  CAS  Google Scholar 

  • Willey JC, Broussoud A, Sleemi A, Bennett WP, Cerutti P, Harris, CC (1991) Immortalization of normal human bronchial epithelial cells by human papillomavirus 16 and 18. Cancer Res 51:5370–5377.

    PubMed  CAS  Google Scholar 

  • Woodworth CD, Simpson S (1993) Comperative lymphokine secretion by cultured normal human cervical keratinocytes, papillomavirus-immortalized, and carcinoma cell lines. Am J Pathol 142:1544–1555.

    PubMed  CAS  Google Scholar 

  • Woodworth CD, Waggoner S, Barnes W, Stoler MH, DiPaolo JA (1990a) Human cervical and foreskin epithelial cells immortalized by human papillomavirus DNAs exhibit dysplastic differentiation in vivo. Cancer Res 50:3709–3715.

    PubMed  CAS  Google Scholar 

  • Woodworth CD, Notario V, DiPaolo JA (1990b) Transforming growth factor beta 1 and 2 transcriptionally regulate human papillomavirus (HPV) type 16 early gene expression in HPV-immortalized human genital epithelial cells. J Virol 64:4767–4775.

    PubMed  CAS  Google Scholar 

  • Woodworth CD, Lichti U, Simpson S, Evans CH, DiPaolo JA (1992) Leukoregulin and gamma-interferon inhibit human papillomavirus type 16 gene transcription in human papil-lomavirus-immortalized human cervical cells. Cancer Res 52:456–463.

    PubMed  CAS  Google Scholar 

  • Yang S, Lickteig RL, Estes R, Rundell K, Walter G, Mumby M (1991) Control of phosphatase 2A by simian virus 40 small t antigen. Mol Cell Biol 11:1988–1995.

    PubMed  CAS  Google Scholar 

  • Yasumoto S, Taniguchi A, Sohma K (1991) Epidermal growth factor (EGF) elicits downregulation of human papillomavirus-type 16 (HPV-16) E6/E7 mRNA at the transcriptional level in an EGF-stimulated human keratinocyte cell line: functional role of EGF-responsive silencer in the HPV-16 long control region. J Virol 65:2000–2009.

    PubMed  CAS  Google Scholar 

  • Yee C, Krishnan-Hewlatt I, Baker C, Schlegel R, Howley P (1985) Presence and expression of human papillomavirus sequences in human cervical carcinoma cell lines. Am J Pathol 119:361–366.

    PubMed  CAS  Google Scholar 

  • zur Hausen H (1975) Oncogenic herpesviruses. Biochem Biophys Acta 417:25–53.

    PubMed  Google Scholar 

  • zur Hausen H (1976) Condylomata acuminata and human genital cancer. Cancer Res 36:530.

    Google Scholar 

  • zur Hausen H (1977a) Human papillomaviruses and their possible role in squamous cell carcinomas. In: Compans RW, Cooper M, Koprowski H et al. (eds) Current topics in microbiology and immunology, vol 78. Springer, Berlin Heidelberg New York, pp1–30.

    Chapter  Google Scholar 

  • zur Hausen H (1977b) Cell-virus gene balance hypothesis of carcinogenesis. Behring Inst Mitt 61:23–30.

    Google Scholar 

  • zur Hausen H (1986) Human genital cancer: synergism between two virus infections or synergysm between a virus infection and initiating events. Lancet 2:1370–1372.

    Google Scholar 

  • zur Hausen H (1986a) Genital papillomavirus infections. In: Rigby PWJ, Wilkie NM (eds) Viruses and Cancer. Cambridge University Press, Cambridge, pp 83–90.

    Google Scholar 

  • zur Hausen H (1989) Papillomaviruses in anogenital cancer as a model to understand the role of viruses in human cancers. Cancer Res 49:4677–4681.

    PubMed  Google Scholar 

  • zur Hausen H (1991 a) Viruses in human cancers. Science 254:1167–1173.

    Article  PubMed  Google Scholar 

  • zur Hausen H (1991b) Papillomavirus/host cell interactions in the pathogenesis of anogenital cancer. In: Brugge J, Curran T, Harlow E, McCormick F (eds) Origins of human cancer. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 685–705.

    Google Scholar 

  • zur Hausen H (1991c) Human papillomaviruses in the pathogenesis of anogenital cancer. Virology 184:9–13.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    H. zur Hausen

Authors
  1. H. zur Hausen
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Deutsches Krebsforschungszentrum, Vorsitzender des Stiftungsrates, Im Neuenheimer Feld 280, D-69120, Heidelberg, Germany

    Harald zur Hausen

Rights and permissions

Reprints and permissions

Copyright information

© 1994 Springer-Verlag Berlin · Heidelberg

About this chapter

Cite this chapter

zur Hausen, H. (1994). Molecular Pathogenesis of Cancer of the Cervix and Its Causation by Specific Human Papillomavirus Types. In: zur Hausen, H. (eds) Human Pathogenic Papillomaviruses. Current Topics in Microbiology and Immunology, vol 186. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-78487-3_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-78487-3_8

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-78489-7

  • Online ISBN: 978-3-642-78487-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation