DOI: 10.1128/jvi.79.23.14899-14908.2005. Skin Hyperproliferation and Susceptibility to Chemical Carcinogenesis in Transgenic Mice Expressing E6 and E7 of Human Papillomavirus Type 38

Skin Hyperproliferation and Susceptibility to Chemical Carcinogenesis in Transgenic Mice Expressing E6 and E7 of Human Papillomavirus Type 38

10.1128/jvi.79.23.14899-14908.2005

Crossref journal-article

American Society for Microbiology

Journal of Virology (235)

Abstract

ABSTRACT The oncoproteins E6 and E7 of human papillomavirus type 38 (HPV38) display several transforming activities in vitro, including immortalization of primary human keratinocytes. To evaluate the oncogenic activities of the viral proteins in an in vivo model, we generated transgenic mice expressing HPV38 E6 and E7 under the control of the bovine homologue of the human keratin 10 (K10) promoter. Two distinct lines of HPV38 E6/E7-expressing transgenic mice that express the viral genes at different levels were obtained. In both lines, HPV38 E6 and E7 induced cellular proliferation, hyperplasia, and dysplasia in the epidermis. The rate of occurrence of these events was proportional to the levels of HPV38 E6 and E7 expression in the two transgenic lines. Exposure of the epidermis of nontransgenic mice to UV led to p21 WAF1 accumulation and cell cycle arrest. In contrast, keratinocytes from transgenic mice continued to proliferate and were not positive for p21 WAF1 , indicating that cell cycle checkpoints are altered in keratinocytes expressing the viral genes. Although the HPV38 E6/E7-expressing transgenic mice did not develop spontaneous tumors during their life span, two-stage carcinogen treatment led to a high incidence of papillomas, keratoacanthomas, and squamous-cell carcinomas in HPV38 mice compared with nontransgenic animals. Together, these data show that HPV38 E6 and E7 display transforming properties in vivo, providing further support for the role of HPV38 in carcinogenesis.

Bibliography

Dong, W., Kloz, U., Accardi, R., Caldeira, S., Tong, W.-M., Wang, Z.-Q., Jansen, L., DuÌrst, M., Sylla, B. S., Gissmann, L., & Tommasino, M. (2005). Skin Hyperproliferation and Susceptibility to Chemical Carcinogenesis in Transgenic Mice Expressing E6 and E7 of Human Papillomavirus Type 38. Journal of Virology, 79(23), 14899â14908.

Authors 11

Wen Dong (first)
Ulrich Kloz (additional)
Rosita Accardi (additional)
Sandra Caldeira (additional)
Wei-Min Tong (additional)
Zhao-Qi Wang (additional)
Lars Jansen (additional)
Matthias Dürst (additional)
Bakary S. Sylla (additional)
Lutz Gissmann (additional)
Massimo Tommasino (additional)

References 36 Referenced 65

10.1128/mcb.14.12.8250-8258.1994
10.1002/j.1460-2075.1989.tb03355.x
10.1038/nrc1253
Boyle, J., R. M. MacKie, J. D. Briggs, B. J. Junor, and T. C. Aitchison. 1984. Cancer warts, and sunshine in renal transplant patients. A case-control study. Lanceti:702-705. / Lancet (1984)
10.1016/j.canlet.2003.12.003
10.1128/JVI.77.3.2195-2206.2003
10.1016/j.virol.2004.03.033
10.1016/0042-6822(92)90688-L
Eckert, R. L., J. F. Crish, S. Balasubramanian, and E. A. Rorke. 2000. Transgenic animal models of human papillomavirus-dependent disease. Int. J. Oncol.16:853-870. / Int. J. Oncol. (2000)
10.3181/00379727-206-43720A
10.1097/00007890-199003000-00006
10.1128/JVI.78.9.4797-4805.2004
10.1128/jvi.62.10.3655-3661.1988
Jablonska, S., J. Dabrowski, and K. Jakubowicz. 1972. Epidermodysplasia verruciformis as a model in studies on the role of papovaviruses in oncogenesis. Cancer Res.32:583-589. / Cancer Res. (1972)
10.1101/gad.182100
10.1006/scbi.1999.0143
10.1158/1055-9965.EPI-04-0551
10.1073/pnas.90.12.5583
10.1074/jbc.M212696200
10.1016/S0738-081X(96)00169-1
10.1128/JVI.78.24.13769-13778.2004
10.1038/sj.onc.1205617
10.1038/sj.onc.1204869
10.1128/JVI.78.21.11451-11460.2004
10.1038/sj.onc.1204860
10.1128/JVI.77.12.6957-6964.2003
Orth, G., S. Jablonska, M. Jarzabek-Chorzelska, S. Obalek, G. Rzesa, M. Favre, and O. Croissant. 1979. Characteristics of the lesions and risk of malignant conversion associated with the type of human papillomavirus involved in epidermodysplasia verruciformis. Cancer Res.39:1074-1082. / Cancer Res. (1979)
Pfister, H. 2003. Chapter 8: human papillomavirus and skin cancer. J. Natl. Cancer Inst. Monogr.31:52-56. / J. Natl. Cancer Inst. Monogr. (2003)
10.1158/0008-5472.CAN-04-3263
10.1006/viro.1999.0106
10.1128/JVI.73.7.5887-5893.1999
10.1111/j.1440-0960.1976.tb00798.x
Walder, B. K., M. R. Robertson, and D. Jeremy. 1971. Skin cancer and immunosuppression. Lancetii:1282-1283. / Lancet (1971)
10.1111/j.0022-202X.2005.23733.x
Yamashita, T., K. Segawa, Y. Fujinaga, T. Nishikawa, and K. Fujinaga. 1993. Biological and biochemical activity of E7 genes of the cutaneous human papillomavirus type 5 and 8. Oncogene8:2433-2441. / Oncogene (1993)
10.1038/nrc798

Dates

Type	When
Created	19 years, 9 months ago (Nov. 10, 2005, 1:12 p.m.)
Deposited	3 years, 5 months ago (March 5, 2022, 4:49 a.m.)
Indexed	11 months, 3 weeks ago (Sept. 9, 2024, 4:28 a.m.)
Issued	19 years, 8 months ago (Dec. 15, 2005)
Published	19 years, 8 months ago (Dec. 15, 2005)
Published Print	19 years, 8 months ago (Dec. 15, 2005)

Funders 0

None

BibTeX

@article{Dong_2005, title={Skin Hyperproliferation and Susceptibility to Chemical Carcinogenesis in Transgenic Mice Expressing E6 and E7 of Human Papillomavirus Type 38}, volume={79}, ISSN={1098-5514}, url={http://dx.doi.org/10.1128/jvi.79.23.14899-14908.2005}, DOI={10.1128/jvi.79.23.14899-14908.2005}, number={23}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Dong, Wen and Kloz, Ulrich and Accardi, Rosita and Caldeira, Sandra and Tong, Wei-Min and Wang, Zhao-Qi and Jansen, Lars and Dürst, Matthias and Sylla, Bakary S. and Gissmann, Lutz and Tommasino, Massimo}, year={2005}, month=dec, pages={14899–14908} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2024,
        9,
        9
      ]
    ],
    "date-time": "2024-09-09T08:28:04Z",
    "timestamp": 1725870484152
  },
  "reference-count": 36,
  "publisher": "American Society for Microbiology",
  "issue": "23",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2005,
            12,
            15
          ]
        ],
        "date-time": "2005-12-15T00:00:00Z",
        "timestamp": 1134604800000
      },
      "content-version": "tdm",
      "delay-in-days": 0,
      "URL": "https://journals.asm.org/non-commercial-tdm-license"
    }
  ],
  "content-domain": {
    "domain": [
      "journals.asm.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2005,
        12,
        15
      ]
    ]
  },
  "abstract": "<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            The oncoproteins E6 and E7 of human papillomavirus type 38 (HPV38) display several transforming activities in vitro, including immortalization of primary human keratinocytes. To evaluate the oncogenic activities of the viral proteins in an in vivo model, we generated transgenic mice expressing HPV38 E6 and E7 under the control of the bovine homologue of the human keratin 10 (K10) promoter. Two distinct lines of HPV38 E6/E7-expressing transgenic mice that express the viral genes at different levels were obtained. In both lines, HPV38 E6 and E7 induced cellular proliferation, hyperplasia, and dysplasia in the epidermis. The rate of occurrence of these events was proportional to the levels of HPV38 E6 and E7 expression in the two transgenic lines. Exposure of the epidermis of nontransgenic mice to UV led to p21\n            <jats:sup>WAF1</jats:sup>\n            accumulation and cell cycle arrest. In contrast, keratinocytes from transgenic mice continued to proliferate and were not positive for p21\n            <jats:sup>WAF1</jats:sup>\n            , indicating that cell cycle checkpoints are altered in keratinocytes expressing the viral genes. Although the HPV38 E6/E7-expressing transgenic mice did not develop spontaneous tumors during their life span, two-stage carcinogen treatment led to a high incidence of papillomas, keratoacanthomas, and squamous-cell carcinomas in HPV38 mice compared with nontransgenic animals. Together, these data show that HPV38 E6 and E7 display transforming properties in vivo, providing further support for the role of HPV38 in carcinogenesis.\n          </jats:p>",
  "DOI": "10.1128/jvi.79.23.14899-14908.2005",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2005,
        11,
        10
      ]
    ],
    "date-time": "2005-11-10T18:12:58Z",
    "timestamp": 1131646378000
  },
  "page": "14899-14908",
  "update-policy": "http://dx.doi.org/10.1128/asmj-crossmark-policy-page",
  "source": "Crossref",
  "is-referenced-by-count": 65,
  "title": "Skin Hyperproliferation and Susceptibility to Chemical Carcinogenesis in Transgenic Mice Expressing E6 and E7 of Human Papillomavirus Type 38",
  "prefix": "10.1128",
  "volume": "79",
  "author": [
    {
      "given": "Wen",
      "family": "Dong",
      "sequence": "first",
      "affiliation": [
        {
          "name": "International Agency for Research on Cancer, World Health Organization, 69372 Lyon Cedex 08, France"
        }
      ]
    },
    {
      "given": "Ulrich",
      "family": "Kloz",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Deutsches Krebsforschungszentrum, D-69120 Heidelberg, Germany"
        }
      ]
    },
    {
      "given": "Rosita",
      "family": "Accardi",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "International Agency for Research on Cancer, World Health Organization, 69372 Lyon Cedex 08, France"
        }
      ]
    },
    {
      "given": "Sandra",
      "family": "Caldeira",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Deutsches Krebsforschungszentrum, D-69120 Heidelberg, Germany"
        }
      ]
    },
    {
      "given": "Wei-Min",
      "family": "Tong",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "International Agency for Research on Cancer, World Health Organization, 69372 Lyon Cedex 08, France"
        }
      ]
    },
    {
      "given": "Zhao-Qi",
      "family": "Wang",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "International Agency for Research on Cancer, World Health Organization, 69372 Lyon Cedex 08, France"
        }
      ]
    },
    {
      "given": "Lars",
      "family": "Jansen",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Gyna\u0308kologische Molekularbiologie Frauenklinik der FSU Jena, Bachstr. 18, D-07743 Jena, Germany"
        }
      ]
    },
    {
      "given": "Matthias",
      "family": "Du\u0308rst",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Gyna\u0308kologische Molekularbiologie Frauenklinik der FSU Jena, Bachstr. 18, D-07743 Jena, Germany"
        }
      ]
    },
    {
      "given": "Bakary S.",
      "family": "Sylla",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "International Agency for Research on Cancer, World Health Organization, 69372 Lyon Cedex 08, France"
        }
      ]
    },
    {
      "given": "Lutz",
      "family": "Gissmann",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Deutsches Krebsforschungszentrum, D-69120 Heidelberg, Germany"
        }
      ]
    },
    {
      "given": "Massimo",
      "family": "Tommasino",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "International Agency for Research on Cancer, World Health Organization, 69372 Lyon Cedex 08, France"
        }
      ]
    }
  ],
  "member": "235",
  "reference": [
    {
      "key": "e_1_3_2_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/mcb.14.12.8250-8258.1994"
    },
    {
      "key": "e_1_3_2_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1989.tb03355.x"
    },
    {
      "key": "e_1_3_2_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nrc1253"
    },
    {
      "key": "e_1_3_2_5_2",
      "first-page": "702",
      "year": "1984",
      "unstructured": "Boyle, J., R. M. MacKie, J. D. Briggs, B. J. Junor, and T. C. Aitchison. 1984. Cancer warts, and sunshine in renal transplant patients. A case-control study. Lanceti:702-705.",
      "journal-title": "Lancet"
    },
    {
      "key": "e_1_3_2_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.canlet.2003.12.003"
    },
    {
      "key": "e_1_3_2_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.77.3.2195-2206.2003"
    },
    {
      "key": "e_1_3_2_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.virol.2004.03.033"
    },
    {
      "key": "e_1_3_2_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0042-6822(92)90688-L"
    },
    {
      "key": "e_1_3_2_10_2",
      "first-page": "853",
      "volume": "16",
      "year": "2000",
      "unstructured": "Eckert, R. L., J. F. Crish, S. Balasubramanian, and E. A. Rorke. 2000. Transgenic animal models of human papillomavirus-dependent disease. Int. J. Oncol.16:853-870.",
      "journal-title": "Int. J. Oncol."
    },
    {
      "key": "e_1_3_2_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.3181/00379727-206-43720A"
    },
    {
      "key": "e_1_3_2_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1097/00007890-199003000-00006"
    },
    {
      "key": "e_1_3_2_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.78.9.4797-4805.2004"
    },
    {
      "key": "e_1_3_2_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.62.10.3655-3661.1988"
    },
    {
      "key": "e_1_3_2_15_2",
      "first-page": "583",
      "volume": "32",
      "year": "1972",
      "unstructured": "Jablonska, S., J. Dabrowski, and K. Jakubowicz. 1972. Epidermodysplasia verruciformis as a model in studies on the role of papovaviruses in oncogenesis. Cancer Res.32:583-589.",
      "journal-title": "Cancer Res."
    },
    {
      "key": "e_1_3_2_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.182100"
    },
    {
      "key": "e_1_3_2_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/scbi.1999.0143"
    },
    {
      "key": "e_1_3_2_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1158/1055-9965.EPI-04-0551"
    },
    {
      "key": "e_1_3_2_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.90.12.5583"
    },
    {
      "key": "e_1_3_2_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M212696200"
    },
    {
      "key": "e_1_3_2_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0738-081X(96)00169-1"
    },
    {
      "key": "e_1_3_2_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.78.24.13769-13778.2004"
    },
    {
      "key": "e_1_3_2_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/sj.onc.1205617"
    },
    {
      "key": "e_1_3_2_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/sj.onc.1204869"
    },
    {
      "key": "e_1_3_2_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.78.21.11451-11460.2004"
    },
    {
      "key": "e_1_3_2_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/sj.onc.1204860"
    },
    {
      "key": "e_1_3_2_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.77.12.6957-6964.2003"
    },
    {
      "key": "e_1_3_2_28_2",
      "first-page": "1074",
      "volume": "39",
      "year": "1979",
      "unstructured": "Orth, G., S. Jablonska, M. Jarzabek-Chorzelska, S. Obalek, G. Rzesa, M. Favre, and O. Croissant. 1979. Characteristics of the lesions and risk of malignant conversion associated with the type of human papillomavirus involved in epidermodysplasia verruciformis. Cancer Res.39:1074-1082.",
      "journal-title": "Cancer Res."
    },
    {
      "key": "e_1_3_2_29_2",
      "first-page": "52",
      "volume": "31",
      "year": "2003",
      "unstructured": "Pfister, H. 2003. Chapter 8: human papillomavirus and skin cancer. J. Natl. Cancer Inst. Monogr.31:52-56.",
      "journal-title": "J. Natl. Cancer Inst. Monogr."
    },
    {
      "key": "e_1_3_2_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1158/0008-5472.CAN-04-3263"
    },
    {
      "key": "e_1_3_2_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/viro.1999.0106"
    },
    {
      "key": "e_1_3_2_32_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/JVI.73.7.5887-5893.1999"
    },
    {
      "key": "e_1_3_2_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1440-0960.1976.tb00798.x"
    },
    {
      "key": "e_1_3_2_34_2",
      "first-page": "1282",
      "year": "1971",
      "unstructured": "Walder, B. K., M. R. Robertson, and D. Jeremy. 1971. Skin cancer and immunosuppression. Lancetii:1282-1283.",
      "journal-title": "Lancet"
    },
    {
      "key": "e_1_3_2_35_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.0022-202X.2005.23733.x"
    },
    {
      "key": "e_1_3_2_36_2",
      "first-page": "2433",
      "volume": "8",
      "year": "1993",
      "unstructured": "Yamashita, T., K. Segawa, Y. Fujinaga, T. Nishikawa, and K. Fujinaga. 1993. Biological and biochemical activity of E7 genes of the cutaneous human papillomavirus type 5 and 8. Oncogene8:2433-2441.",
      "journal-title": "Oncogene"
    },
    {
      "key": "e_1_3_2_37_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nrc798"
    }
  ],
  "container-title": "Journal of Virology",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://journals.asm.org/doi/pdf/10.1128/JVI.79.23.14899-14908.2005",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://journals.asm.org/doi/pdf/10.1128/JVI.79.23.14899-14908.2005",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2022,
        3,
        5
      ]
    ],
    "date-time": "2022-03-05T09:49:30Z",
    "timestamp": 1646473770000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://journals.asm.org/doi/10.1128/JVI.79.23.14899-14908.2005"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2005,
        12,
        15
      ]
    ]
  },
  "references-count": 36,
  "journal-issue": {
    "issue": "23",
    "published-print": {
      "date-parts": [
        [
          2005,
          12,
          15
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1128/JVI.79.23.14899-14908.2005"
  ],
  "URL": "http://dx.doi.org/10.1128/JVI.79.23.14899-14908.2005",
  "relation": {
    "has-review": [
      {
        "id-type": "doi",
        "id": "10.3410/f.8245.465725",
        "asserted-by": "object"
      }
    ]
  },
  "ISSN": [
    "0022-538X",
    "1098-5514"
  ],
  "subject": [],
  "container-title-short": "J Virol",
  "published": {
    "date-parts": [
      [
        2005,
        12,
        15
      ]
    ]
  },
  "assertion": [
    {
      "value": "2005-06-13",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2005-09-14",
      "order": 1,
      "name": "accepted",
      "label": "Accepted",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2005-12-15",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}