Skip to main content
SpringerLink
Log in

Induction of focal epithelial hyperplasia in tongue of young bk6-E6/E7 HPV16 transgenic mice

  • Original Paper
  • Published:
Transgenic Research Aims and scope Submit manuscript

Abstract

Squamous cell carcinoma (SCC) of the oral cavity is one of the most common neoplasms in the world. During the past 2 decades, the role of high-risk human papilloma virus (HR-HPV) has been studied and the data supporting HPV as a one of the causative agents in the development and progression of a sub-set of head and neck squamous cell carcinomas (HNSCC) has accumulated. In order to investigate the role of HR-HPV oncogene expression in early epithelial alterations in vivo, we produced transgenic mice expressing HPV16 early region genes from the promoter of the bovine keratin 6 gene (Tg[bK6-E6/E7]). In this article, we demonstrate that E6/E7 transgene was abundantly expressed and cellular proliferation was increased in the middle tongue epithelia of transgenic mice, and that in the same region young (27 weeks old) Tg[bK6-E6/E7] mice spontaneously developed histological alterations, mainly focal epithelial hyperplasia (FEH).

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Badaracco G, Venuti A, Morello R, Muller A, Marcante ML (2000) Human papillomavirus in head and neck carcinomas: prevalence, physical status and relationship with clinical/pathological parameters. Anticancer Res 20:1301–1305

    PubMed  CAS  Google Scholar 

  • Bailleul B, Surani MA, White S, Barton SC, Brown K, Blessing M, Jorcano J, Balmain A (1990) Skin hyperkeratosis and papilloma formation in transgenic mice expressing a ras oncogene from a suprabasal keratin promoter. Cell 62:697–708. doi:10.1016/0092-8674(90)90115-U

    Article  PubMed  CAS  Google Scholar 

  • Binnie WH, Rankin KV, Mackenzie IC (1983) Etiology of oral squamous cell carcinoma. J Oral Pathol 12:11–29. doi:10.1111/j.1600-0714.1983.tb00312.x

    Article  PubMed  CAS  Google Scholar 

  • Blessing M, Nanney LB, King LE, Jones CM, Hogan BL (1993) Transgenic mice as a model to study the role of TGF-beta-related molecules in hair follicles. Genes Dev 7:204–215. doi:10.1101/gad.7.2.204

    Article  PubMed  CAS  Google Scholar 

  • Blons H, Laurent-Puig P (2003) TP53 and head and neck neoplasms. Hum Mutat 21:252–257. doi:10.1002/humu.10171

    Article  PubMed  CAS  Google Scholar 

  • Blot WJ, McLaughlin JK, Devesa SS, Fraumeni JF Jr (1996) Cancers of the oral cavity and pharynx. In: Schottenfeld D, Fraumeni JF Jr (eds) Cancer epidemiology and prevention. Oxford University Press, New York, pp 666–680

    Google Scholar 

  • Bouda M, Gorgoulis VG, Kastrinakis NG, Giannoudis A, Tsoli E, Danassi-Afentaki D, Foukas P, Kyroudi A, Laskaris G, Herrington CS, Kittas C (2000) “High risk” HPV types are frequently detected in potentially malignant and malignant oral lesions, but not in normal oral mucosa. Mod Pathol 13:644–653. doi:10.1038/modpathol.3880113

    Article  PubMed  CAS  Google Scholar 

  • Braakhuis BJ, Snijders PJ, Keune WJ, Meijer CJ, Ruijter-Schippers HJ, Leemans CR, Brakenhoff RH (2004) Genetic patterns in head and neck cancers that contain or lack transcriptionally active human papillomavirus. J Natl Cancer Inst 96:998–1006

    Article  PubMed  CAS  Google Scholar 

  • Campisi G, Panzarella V, Giuliani M, Lajolo C, Di Fede O, Falaschini S, Di Liberto C, Scully C, Lo Muzio L (2007) Human papillomavirus: its identity and controversial role in oral oncogenesis, premalignant and malignant lesions. Int J Oncol 30(4):813–823

    PubMed  CAS  Google Scholar 

  • Capone RB, Pai SI, Koch WM, Gillison ML, Danish HN, Westra WH, Daniel R, Shah KV, Sidransky D (2000) Detection and quantitation of human papillomavirus (HPV) DNA in the sera of patients with HPV associated head and neck squamous cell carcinoma. Clin Cancer Res 6:4171–4175

    PubMed  CAS  Google Scholar 

  • Carlos R, Sedano HO (1994) Multifocal papilloma virus epithelial hyperplasia. Oral Surg Oral Med Oral Pathol 77:631–635. doi:10.1016/0030-4220(94)90325-5

    Article  PubMed  CAS  Google Scholar 

  • Comerford SA, Maika SD, Laimins LA, Messing A, Elsasser HP, Hammer RE (1995) E6 and E7 expression from the HPV 18 LCR: development of genital hyperplasia and neoplasia in transgenic mice. Oncogene 2:587–597

    Google Scholar 

  • Coulombe PA, Kopan R, Fuchs E (1989) Expression of keratin K14 in the epidermis and hair follicle: insights into complex programs of differentiation. J Cell Biol 109:2295–2312. doi:10.1083/jcb.109.5.2295

    Article  PubMed  CAS  Google Scholar 

  • Dahlgren L, Mellin H, Wangsa D, Heselmeyer-Haddad K, Bjornestal L, Lindholm J, Munck-Wikland E, Auer G, Ried T, Dalianis T (2003) Comparative genomic hybridization analysis of tonsillar cancer reveals a different pattern of genomic imbalances in human papillomavirus- positive and -negative tumors. Int J Cancer 107:244–249. doi:10.1002/ijc.11371

    Article  PubMed  CAS  Google Scholar 

  • Dahlgren L, Dahlstrand HM, Lindquist D, Hogmo A, Bjornestal L, Lindholm J, Lundberg B, Dalianis T, Munck-Wikland E (2004) Human papillomavirus is more common in base of tongue than in mobile tongue cancer and is a favorable prognostic factor in base of tongue cancer patients. Int J Cancer 20:1015–1019. doi:10.1002/ijc.20490

    Article  CAS  Google Scholar 

  • Dai M, Clifford GM, le Calvez F, Castellsagué X, Snijders PJ, Pawlita M, Herrero R, Hainaut P, Franceschi S (2004) Human papillomavirus type 16 and TP53 mutation in oral cancer: matched analysis of the IARC multicenter study. Cancer Res 64:468–471. doi:10.1158/0008-5472.CAN-03-3284

    Article  PubMed  CAS  Google Scholar 

  • Dehn D, Torkko KC, Shroyer KR (2007) Human papillomavirus testing and molecular markers of cervical dysplasia and carcinoma. Cancer 111(1):1–14. doi:10.1002/cncr.22425

    Article  PubMed  CAS  Google Scholar 

  • Demers GW, Halbert GallowayDA (1994) Elevated wild-type p53 protein levels in human epithelial cell lines immortalized by the human papillomavirus type 16 E7 gene. Virology 198:169–174. doi:10.1006/viro.1994.1019

    Article  PubMed  CAS  Google Scholar 

  • Doorbar J (2006) Molecular biology of human papillomavirus infection and cervical cancer. Clin Sci (Lond) 110:525–541. doi:10.1042/CS20050369

    CAS  Google Scholar 

  • Du M, Fan X, Hanada T, Gao H, Lutchman M, Brandsma JL, Chishti AH, Chen JJ (2005) Association of cottontail rabbit papillomavirus E6 oncoproteins with the hDlg/SAP97 tumor suppressor. J Cell Biochem 94:1038–1045. doi:10.1002/jcb.20383

    Article  PubMed  CAS  Google Scholar 

  • Dyson N, Howley PM, Munger K, Harlow E (1989) The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science 243:934–937. doi:10.1126/science.2537532

    Article  PubMed  CAS  Google Scholar 

  • Escalante-Alcalde D, Recillas-Targa F, Valencia C, Santa-Olalla J, Chavez P, Marroquin A, Gutierrez X, Gariglio P, Covarrubias L (2000) Expression of E6 and E7 papillomavirus oncogenes in the outer root sheath of hair follicles extends the growth phase and bypasses resting at telogen. Cell Growth Differ 11:527–539

    PubMed  CAS  Google Scholar 

  • Franceschi S, Munoz N, Bosch XF, Snijders PJ, Walboomers JM (1996) Human papillomavirus and cancers of the upper aerodigestive tract: a review of epidemiological and experimental evidence. Cancer Epidemiol Biomarkers Prev 5:567–575

    PubMed  CAS  Google Scholar 

  • Frisch M, Biggar RJ (1999) Aetiological parallel between tonsillar and anogenital squamous-cell carcinomas. Lancet 354:1442–1443. doi:10.1016/S0140-6736(99)92824-6

    Article  PubMed  CAS  Google Scholar 

  • Fujinaga Y, Shimada M, Okazawa K, Fukushima M, Kato I, Fujinaga K (1991) Simultaneous detection and typing of genital human papillomavirus DNA using the polymerase chain reaction. J Gen Virol 72:1039–1044. doi:10.1099/0022-1317-72-5-1039

    Article  PubMed  CAS  Google Scholar 

  • Gavrieli Y, Sherman Y, Ben-Sasson SA (1992) Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 119:493–501. doi:10.1083/jcb.119.3.493

    Article  PubMed  CAS  Google Scholar 

  • Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, Zahurak ML, Daniel RW, Viglione M, Symer DE, Shah KV, Sidransky D (2000) Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 92:709–720. doi:10.1093/jnci/92.9.709

    Article  PubMed  CAS  Google Scholar 

  • Gillison ML, Shah KV (2001) Human papillomavirus-associated head and neck squamous cell carcinoma: mounting evidence for an etiologic role for human papillomavirus in a subset of head and neck cancers. Curr Opin Oncol 13:183–188. doi:10.1097/00001622-200105000-00009

    Article  PubMed  CAS  Google Scholar 

  • Griep AE, Herber R, Jeon S, Lohse JK, Dubielzig RR, Lambert PF (1993) Tumorigenicity by human papillomavirus type 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 

  • Guo L, Yu QC, Fuchs E (1993) Targeting expression of keratinocyte growth factor to keratinocytes elicits striking changes in epithelial differentiation in transgenic mice. EMBO J 12:973–986

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70. doi:10.1016/S0092-8674(00)81683-9

    Article  PubMed  CAS  Google Scholar 

  • Herrero R, Castellsagué X, Pawlita M, Lissowska J, Kee F, Balaram P, Rajkumar T, Sridhar H, Rose B, Pintos J, Fernández L, Idris A, Sánchez MJ, Nieto A, Talamini R, Tavani A, Bosch FX, Reidel U, Snijders PJ, Meijer CJ, Viscidi R, Muñoz N, Franceschi S (2003) Human papillomavirus and oral cancer: the International Agency for Research on Cancer multicenter study. J Natl Cancer Inst 95:1772–1783

    PubMed  Google Scholar 

  • Hong Y, Yang L, Li C, Xia H, Rhodus NL, Cheng B (2007) Frequent mutation of p16(CDKN2A) exon 1 during rat tongue carcinogenesis induced by 4-nitroquinoline-1-oxide. Mol Carcinog 46:85–90. doi:10.1002/mc.20197

    Article  PubMed  CAS  Google Scholar 

  • Howes KA, Ransom N, Papermaster DS, Lasudry JG, Albert DM, Windle JJ (1994) Apoptosis or retinoblastoma: alternative fates of photoreceptors expressing the HPV-16 E7 gene in the presence or absence of p53. Genes Dev 8:1300–1310. doi:10.1101/gad.8.11.1300

    Article  PubMed  CAS  Google Scholar 

  • Huibregtse JM, Scheffner M, Howley PM (1994) E6-AP directs the HPV E6-dependent inactivation of p53 and is representative of a family of structurally and functionally related proteins. Cold Spring Harb Symp Quant Biol 59:237–245

    PubMed  CAS  Google Scholar 

  • Ide F, Oda H, Nakatsuru Y, Kusama K, Sakashita H, Tanaka K, Ishikawa T (2001) Xeroderma pigmentosum group A gene action as a protection factor against 4-nitroquinoline 1-oxide-induced tongue carcinogenesis. Carcinogenesis 22:567–572. doi:10.1093/carcin/22.4.567

    Article  PubMed  CAS  Google Scholar 

  • Koskinen WJ, Chen RW, Leivo I, Makitie A, Back L, Kontio R, Suuronen R, Lindqvist C, Auvinen E, Molijn A, Quint WG, Vaheri A, Aaltonen LM (2003) Prevalence and physical status of human papillomavirus in squamous cell carcinomas of the head and neck. Int J Cancer 107:401–406. doi:10.1002/ijc.11381

    Article  PubMed  CAS  Google Scholar 

  • Kreimer AR, Clifford GM, Boyle P, Franceschi S (2005) Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev 14(2):467–475. doi:10.1158/1055-9965.EPI-04-0551

    Article  PubMed  CAS  Google Scholar 

  • Lambert PF, Pan H, Pitot HC, Liem A, Jackson M, Griep AE (1993) Epidermal cancer associated with expression of human papillomavirus type 16 E6 and E7 oncogenes in the skin of transgenic mice. Proc Natl Acad Sci USA 90:5583–5587. doi:10.1073/pnas.90.12.5583

    Article  PubMed  CAS  Google Scholar 

  • Manjarrez ME, Ocadiz R, Valle L, Pacheco C, Marroquin A, De la Torre C, Selman M, Gariglio P (2006) Detection of human papillomavirus and relevant tumor suppressors and oncoproteins in laryngeal tumors. Clin Cancer Res 12(23):6946–6951. doi:10.1158/1078-0432.CCR-06-1214

    Article  PubMed  CAS  Google Scholar 

  • Martinez A, Miller MJ, Quinn K, Unsworth EJ, Ebina M, Cutita F (1995) Non-radiactive localization of nucleic acids by direct in situ PCR and in situ RT-PCR in paraffin-embedded sections. J Histochem Cytochem 43:739–747

    PubMed  CAS  Google Scholar 

  • Martinez A (1998) Detection of mRNA in tissue sections by in situ RT-PCR. Cell Vis 5:70

    Google Scholar 

  • Matsumoto Y, Nakagawa S, Yano T, Takizawa S, Nagasaka K, Nakagawa K, Minaguchi T, Wada O, Ooishi H, Matsumoto K, Yasugi T, Kanda T, Huibregtse JM, Taketani Y (2006) 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 78:501–507. doi:10.1002/jmv.20568

    Article  PubMed  CAS  Google Scholar 

  • Matzow T, Boysen M, Kalantari M, Johansson B, Hagmar B (1998) Low detection rate of HPV in oral and laryngeal carcinomas. Acta Oncol 37:73–76. doi:10.1080/028418698423203

    Article  PubMed  CAS  Google Scholar 

  • McKaig RG, Baric RS, Olhsan AF (1998) Human papillomavirus and head neck cancer: epidemiology and molecular biology. Head Neck 20:250–265. doi:10.1002/(SICI)1097-0347(199805)20:3<250::AID-HED11>3.0.CO;2-O

    Google Scholar 

  • Mellin H, Friesland S, Lewensohn R, Dalianis T, Munck-Wikland E (2000) Human papillomavirus (HPV) DNA in tonsillar cancer: clinical correlates, risk of relapse, and survival. Int J Cancer 89:300–304. doi:10.1002/1097-0215(20000520)89:3<300::AID-IJC14>3.0.CO;2-G

    Google Scholar 

  • Mellin H, Dahlgren L, Munck-Wikland E, Lindholm J, Rabbani H, Kalantari M, Dalianis T (2002) Human papillomavirus type 16 is episomal and a high viral load may be correlated to better prognosis in tonsillar cancer. Int J Cancer 102:152–158. doi:10.1002/ijc.10669

    Article  PubMed  CAS  Google Scholar 

  • Mellin H, Friesland S, Auer G, Dalianis T, Munck-Wikland E (2003) Human papillomavirus and DNA ploidy in tonsillar cancer—correlation to prognosis. Anticancer Res 23:2821–2828

    PubMed  Google Scholar 

  • Mork J, Lie AK, Glattre E, Hallmans G, Jellum E, Koskela P, Moller B, Pukkala E, Schiller JT, Youngman L, Lehtinen M, Dillner J (2001) Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. N Engl J Med 344:1125–1131. doi:10.1056/NEJM200104123441503

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  Google Scholar 

  • Münger K, Baldwin A, Edwards EM, Hayakawa H (2004) Mechanisms of human papillomavirus-induced oncogenesis. J Virol 78:11451–11460. doi:10.1128/JVI.78.21.11451-11460.2004

    Article  PubMed  CAS  Google Scholar 

  • Navarro JM, Casatorres J, Jorcano JL (1995) Elements controlling the expression and induction of the skin hyperproliferation-associated keratin K6. J Biol Chem 270:21362–21367. doi:10.1074/jbc.270.36.21362

    Article  PubMed  CAS  Google Scholar 

  • Neville BW, Day TA (2002) Oral cancer and precancerous lesions. CA Cancer J Clin 52:195–215

    Article  PubMed  Google Scholar 

  • Nohara O, Gilchrist M, Déry RE, Stenton GR, Hirji NS, Befus AD (1999) Reverse transcriptase in situ polymerase chain reaction for gene expression in rat mast cells and macrophages. J Immunol Methods 226:147–158. doi:10.1016/S0022-1759(99)00061-7

    Article  PubMed  CAS  Google Scholar 

  • Nuovo GJ (1996) PCR in situ hybridization protocols and applications. De Lippincott-Raven, New York

    Google Scholar 

  • Nuovo GJ (2001) Co-labeling using in situ PCR: a review. J Histochem Cytochem 49:1329–1339

    PubMed  CAS  Google Scholar 

  • Nuovo GJ (2006) The surgical and cytopathology of viral infections: utility of immunohistochemistry, in situ hybridization, and in situ polymerase chain reaction amplification. Ann Diagn Pathol 10:117–131. doi:10.1016/j.anndiagpath.2006.02.003

    Article  PubMed  Google Scholar 

  • Nuovo GJ (2007) The utility of in situ-based methodologies including in situ polymerase chain reaction for the diagnosis and study of viral infections. Hum Pathol 38:1123–1136. doi:10.1016/j.humpath.2007.04.005

    Article  PubMed  CAS  Google Scholar 

  • Ocadiz-Delgado R, Castaneda-Saucedo E, Indra AK, Hernandez-Pando R, Gariglio P (2008) Impaired cervical homeostasis upon selective ablation of RXRalpha in epithelial cells. Genesis 46:19–28. doi:10.1002/dvg.20357

    Article  PubMed  CAS  Google Scholar 

  • Opitz OG, Harada H, Suliman Y, Rhoades B, Sharpless NE, Kent R, Kopelovich L, Nakagawa H, Rustgi AK (2002) A mouse model of human oral-esophageal cancer. J Clin Invest 110:761–769

    PubMed  CAS  Google Scholar 

  • Pan H, Griep AE (1994) Altered cell cycle regulation in the lens of HPV-16 E6 or E7 transgenic mice: implications for tumor suppressor gene function in development. Genes Dev 8:1285–1299. doi:10.1101/gad.8.11.1285

    Article  PubMed  CAS  Google Scholar 

  • Pan H, Griep AE (1995) Temporally distinct patterns of p53-dependent and p53-independent apoptosis during mouse lens development. Genes Dev 9:2157–2169. doi:10.1101/gad.9.17.2157

    Article  PubMed  CAS  Google Scholar 

  • Parkin SM, Pisani P, Ferlay J (1993) Estimates of worldwide incidence of eighteen major cancers. Int J Cancer 54:594–606. doi:10.1002/ijc.2910540413

    Article  PubMed  CAS  Google Scholar 

  • Patel V, Leethanakul C, Gutkind JS (2001) New approaches to the understanding of the molecular basis of oral cancer. Crit Rev Oral Biol Med 12:55–63

    Article  PubMed  CAS  Google Scholar 

  • Ragin CC, Taioli E (2007) Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: review and meta-analysis. Int J Cancer 121(8):1813–1820. doi:10.1002/ijc.22851

    Article  PubMed  CAS  Google Scholar 

  • Reznikoff CA, Belair C, Savelieva E, Zhai Y, Pfeifer K, Yeager T, Thompson KJ, DeVries S, Bindley C, Newton MA, Sekhon G, Walkman F (1994) Long-term genome stability and minimal genotypic and phenotypic alterations in HPV16 E7-, but not E6-, immortalized human uroepithelial cells. Genes Dev 8:2227–2240. doi:10.1101/gad.8.18.2227

    Article  PubMed  CAS  Google Scholar 

  • Riley RR, Duensing S, Brake T, Munger K, Lambert PF, Arbeit JM (2003) Dissection of human papillomavirus E6 and E7 function in transgenic mouse models of cervical carcinogenesis. Cancer Res 63:4862–4871

    PubMed  CAS  Google Scholar 

  • Ringstrom E, Peters E, Hasegawa M, Posner M, Liu M, Kelsey KT (2002) Human papillomavirus type 16 and squamous cell carcinoma of the head and neck. Clin Cancer Res 8:3187–3192

    PubMed  Google Scholar 

  • Ritchie JM, Smith EM, Summersgill KF, Hoffman HT, Wang D, Klussmann JP, Turek LP, Haugen TH (2003) Human papillomavirus infection as a prognostic factor in carcinomas of the oral cavity and oropharynx. Int J Cancer 104:336–344. doi:10.1002/ijc.10960

    Article  PubMed  CAS  Google Scholar 

  • Rothnagel JA, Seki T, Ogo M, Longley MA, Wojcik SM, Bundman DS, Bickenbach JR, Roop DR (1999) The mouse keratin 6 isoforms are differentially expressed in the hair follicle, footpad, tongue and activated epidermis. Differentiation 65:119–130. doi:10.1046/j.1432-0436.1999.6520119.x

    Article  PubMed  CAS  Google Scholar 

  • Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York

    Google Scholar 

  • Sasagawa T, Inoue M, Inoue H, Yutsudo M, Tanizawa O, Hakura A (1992) Induction of uterine cervical neoplasias in mice by human papillomavirus type 16 E6/E7 genes. Cancer Res 52:4420–4426

    PubMed  CAS  Google Scholar 

  • Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM (1990) The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63:1129–1136. doi:10.1016/0092-8674(90)90409-8

    Article  PubMed  CAS  Google Scholar 

  • Scholes AG, Liloglou T, Snijders PJ, Hart CA, Jones AS, Woolgar JA, Vaughan ED, Walboomers JM, Field JK (1997) p53 Mutations in relation to human papillomavirus type 16 infection in squamous cell carcinomas of the head and neck. Int J Cancer 71:796–799. doi:10.1002/(SICI)1097-0215(19970529)71:5<796::AID-IJC17>3.0.CO;2-6

    Google Scholar 

  • Schwartz SM, Daling JR, Doody DR, Wipf GC, Carter JJ, Madeleine MM, Mao EJ, Fitzgibbons ED, Huang S, Beckmann AM, McDougall JK, Galloway DA (1998) Oral cancer risk in relation to sexual history and evidence of human papillomavirus infection. J Natl Cancer Inst 90:1626–1636. doi:10.1093/jnci/90.21.1626

    Article  PubMed  CAS  Google Scholar 

  • Sciubba JJ (2001) Oral cancer. The importance of early diagnosis and treatment. Am J Clin Dermatol 2:239–251. doi:10.2165/00128071-200102040-00005

    Article  PubMed  CAS  Google Scholar 

  • Scully C (2002) Oral squamous cell carcinoma; from an hypothesis about a virus, to concern about possible sexual transmission. Oral Oncol 38:227–234. doi:10.1016/S1368-8375(01)00098-7

    Article  PubMed  Google Scholar 

  • Shibuya K, Mathers CD, Boschi-Pinto C, Lopez AD, Murray CJ (2002) Global and regional estimates of cancer mortality and incidence by site: II. Results for the global burden of disease 2000. BMC Cancer 2(1):37. doi:10.1186/1471-2407-2-37

    Article  PubMed  Google Scholar 

  • Segura-Saint-Gerons R, Toro-Rojas M, Ceballos-Salobreña A, Aparicio-Soria JL, Fuentes-Vaamonde H (2005) Focal epithelial hyperplasia. A rare disease in our area. Med Oral Patol Oral Cir Bucal 10:128–131

    PubMed  Google Scholar 

  • Smith EM, Ritchie JM, Summersgill KF, Klussmann JP, Lee JH, Wang D, Haugen TH, Turek LP (2004) Age, sexual behavior and human papillomavirus infection in oral cavity and oropharyngeal cancers. Int J Cancer 108:766–772. doi:10.1002/ijc.11633

    Article  PubMed  CAS  Google Scholar 

  • Takahashi K, Yan B, Yamanishi K, Imamura S, Coulombe PA (1998) The two functional keratin 6 genes of mouse are differentially regulated and evolved independently from their human orthologs. Genomics 53:170–183. doi:10.1006/geno.1998.5476

    Article  PubMed  CAS  Google Scholar 

  • Takizawa S, Nagasaka K, Nakagawa S, Yano T, Nakagawa K, Yasugi T, Takeuchi T, Kanda T, Huibregtse JM, Akiyama T, Taketani Y (2006) 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 11:453–464. doi:10.1111/j.1365-2443.2006.00954.x

    Article  PubMed  CAS  Google Scholar 

  • Tanaka T, Kojima T, Morishita Y, Mori H (1992) Inhibitory effects of the natural products indole-3-carbinol and sinigrin during initiation and promotion phases of 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis. Jpn J Cancer Res 83:835–842

    PubMed  CAS  Google Scholar 

  • Tanaka T, Kojima T, Kawamori T, Wang A, Suzui M, Okamoto K, Mori H (1993) Inhibition of 4-nitroquinoline-1-oxide-induced rat tongue carcinogenesis by the naturally occurring plant phenolics caffeic, ellagic, chlorogenic and ferulic acids. Carcinogenesis 14:1321–1325. doi:10.1093/carcin/14.7.1321

    Article  PubMed  CAS  Google Scholar 

  • van Houten VM, Snijders PJ, van den Brekel MW, Kummer JA, Meijer CJ, van Leeuwen B, Denkers F, Smeele LE, Snow GB, Brakenhoff RH (2001) Biological evidence that human papillomaviruses are etiologically involved in a subgroup of head and neck squamous cell carcinomas. Int J Cancer 93:232–235. doi:10.1002/ijc.1313

    Article  PubMed  Google Scholar 

  • Valencia C, Bonilla-Delgado J, Oktaba K, Ocádiz-Delgado R, Gariglio P, Covarrubias L (2008) Human papillomavirus E6/E7 oncogenes promote mouse ear regeneration by increasing the rate of wound re-epithelization and epidermal growth. J Invest Dermatol [Epub ahead of print]

  • Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Muñoz N (1999) Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189:12–19. doi:10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F

    Google Scholar 

  • Wiest T, Schwarz E, Enders C, Flechtenmacher C, Bosch FX (2002) Involvement of intact HPV16 E6/E7 gene expression in head and neck cancers with unaltered p53 status and perturbed pRb cell cycle control. Oncogene 21:1510–1517. doi:10.1038/sj.onc.1205214

    Article  PubMed  CAS  Google Scholar 

  • Wojcik SM, Bundman DS, Roop DR (2000) Delayed wound healing in keratin 6a knockout mice. Mol Cell Biol 20:5248–5255. doi:10.1128/MCB.20.14.5248-5255.2000

    Article  PubMed  CAS  Google Scholar 

  • Yamamoto Y, Itoh T, Takahashi H (1994) Assessment of bromodeoxyuridine-labeled S-phase cells in experimentally induced precancerous lesions in the rat’s tongue. Eur Arch Otorhinolaryngol 251:160–164. doi:10.1007/BF00181828

    Article  PubMed  CAS  Google Scholar 

  • Zeitler J, Hsu CP, Dionne H, Bilder D (2004) Domains controlling cell polarity and proliferation in the Drosophila tumor suppressor Scribble. J Cell Biol 167:1137–1146. doi:10.1083/jcb.200407158

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank Biol. Elizabeth Alvarez-Rios, Biol. Enrique García-Villa, M.Sc. María Guadalupe Aguilar González, Mr. Francisco Garzon, Mr. Miguel A. Escobar and Mr. Lauro Macias (CINVESTAV-IPN, Mexico) for technical support. This work was supported by CONACyT (Mexico) and ICGEB, CRP Programme, Trieste, Italy. PG was supported by a UICC Translational Cancer Research Fellowship, funded by Novartis (Switzerland).

Author information

Authors and Affiliations

  1. Department of Genetics & Molecular Biology, CINVESTAV-IPN Mexico, Av. IPN 2508. Colonia San Pedro Zacatenco, CP 07360, Mexico, DF, Mexico

    Rodolfo Ocadiz-Delgado, Alberto Marroquin-Chavira & Patricio Gariglio

  2. Department of Pathology, Hospital Infantil de Mexico “Federico Gómez”, Mexico, Dr. Marquez 162. Col. Doctores, CP 06720, Mexico, DF, Mexico

    Ruth Hernandez-Mote

  3. Institute of Biotechnology-UNAM Mexico, Av. Universidad 2001. Col. Chamilpa, CP 62210, Cuernavaca, Morelos, Mexico

    Concepción Valencia & Luis Covarrubias

  4. Instituto Nacional de Enfermedades Respiratorias (INER), Mexico, Calzada de Tlalpan 4502. Col. Sección XVI, CP 14080, Mexico, DF, Mexico

    M. Eugenia Manjarrez-Zavala

Authors
  1. Rodolfo Ocadiz-Delgado
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alberto Marroquin-Chavira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ruth Hernandez-Mote
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Concepción Valencia
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Eugenia Manjarrez-Zavala
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Luis Covarrubias
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Patricio Gariglio
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Patricio Gariglio.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ocadiz-Delgado, R., Marroquin-Chavira, A., Hernandez-Mote, R. et al. Induction of focal epithelial hyperplasia in tongue of young bk6-E6/E7 HPV16 transgenic mice. Transgenic Res 18, 513–527 (2009). https://doi.org/10.1007/s11248-009-9243-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11248-009-9243-6

Keywords

Search

Navigation