Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Jan;86(2):563–567. doi: 10.1073/pnas.86.2.563

Differential effects of human papillomavirus type 6, 16, and 18 DNAs on immortalization and transformation of human cervical epithelial cells.

G Pecoraro 1, D Morgan 1, V Defendi 1
PMCID: PMC286512  PMID: 2463631

Abstract

The human papillomaviruses (HPVs) are associated with specific benign and malignant lesions of the skin and mucosal epithelia. Cloned viral DNAs from HPV types 6b, 16, and 18 associated with different pathological manifestations of genital neoplasia in vivo were introduced into primary human cervical epithelial cells by electroporation. Cells transfected with HPV16 or HPV18 DNA acquired indefinite lifespans, distinct morphological alterations, and anchorage-independent growth (HPV18), and contain integrated transcriptionally active viral genomes. HPV6b or plasmid electroporated cells senesced at low passage. The alterations in growth and differentiation of the cells appear to reflect the progressive oncogenic processes that result in cervical carcinoma in vivo.

Full text

PDF
563

Images in this article

564Image
on p.564
564Image
on p.564
564Image
on p.564
565Image
on p.565
565Image
on p.565
565Image
on p.565
565Image
on p.565
566Image
on p.566
566Image
on p.566
566Image
on p.566
566Image
on p.566

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BANGLE R., Jr, BERGER M., LEVIN M. VARIATIONS IN THE MORPHOGENESIS OF SQUAMOUS CARCINOMA OF THE CERVIX. Cancer. 1963 Sep;16:1151–1159. doi: 10.1002/1097-0142(196309)16:9<1151::aid-cncr2820160909>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
  2. Beaudenon S., Kremsdorf D., Croissant O., Jablonska S., Wain-Hobson S., Orth G. A novel type of human papillomavirus associated with genital neoplasias. Nature. 1986 May 15;321(6067):246–249. doi: 10.1038/321246a0. [DOI] [PubMed] [Google Scholar]
  3. Bedell M. A., Jones K. H., Laimins L. A. The E6-E7 region of human papillomavirus type 18 is sufficient for transformation of NIH 3T3 and rat-1 cells. J Virol. 1987 Nov;61(11):3635–3640. doi: 10.1128/jvi.61.11.3635-3640.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boshart M., Gissmann L., Ikenberg H., Kleinheinz A., Scheurlen W., zur Hausen H. A new type of papillomavirus DNA, its presence in genital cancer biopsies and in cell lines derived from cervical cancer. EMBO J. 1984 May;3(5):1151–1157. doi: 10.1002/j.1460-2075.1984.tb01944.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Boukamp P., Rupniak H. T., Fusenig N. E. Environmental modulation of the expression of differentiation and malignancy in six human squamous cell carcinoma cell lines. Cancer Res. 1985 Nov;45(11 Pt 2):5582–5592. [PubMed] [Google Scholar]
  6. Chang S. E. In vitro transformation of human epithelial cells. Biochim Biophys Acta. 1986;823(3):161–194. doi: 10.1016/0304-419x(86)90001-6. [DOI] [PubMed] [Google Scholar]
  7. Di Luca D., Pilotti S., Stefanon B., Rotola A., Monini P., Tognon M., De Palo G., Rilke F., Cassai E. Human papillomavirus type 16 DNA in genital tumours: a pathological and molecular analysis. J Gen Virol. 1986 Mar;67(Pt 3):583–589. doi: 10.1099/0022-1317-67-3-583. [DOI] [PubMed] [Google Scholar]
  8. Dürst M., Dzarlieva-Petrusevska R. T., Boukamp P., Fusenig N. E., Gissmann L. Molecular and cytogenetic analysis of immortalized human primary keratinocytes obtained after transfection with human papillomavirus type 16 DNA. Oncogene. 1987;1(3):251–256. [PubMed] [Google Scholar]
  9. Dürst M., Gissmann L., Ikenberg H., zur Hausen H. A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3812–3815. doi: 10.1073/pnas.80.12.3812. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fuchs P. G., Girardi F., Pfister H. Human papillomavirus DNA in normal, metaplastic, preneoplastic and neoplastic epithelia of the cervix uteri. Int J Cancer. 1988 Jan 15;41(1):41–45. doi: 10.1002/ijc.2910410109. [DOI] [PubMed] [Google Scholar]
  11. Gissmann L., Wolnik L., Ikenberg H., Koldovsky U., Schnürch H. G., zur Hausen H. Human papillomavirus types 6 and 11 DNA sequences in genital and laryngeal papillomas and in some cervical cancers. Proc Natl Acad Sci U S A. 1983 Jan;80(2):560–563. doi: 10.1073/pnas.80.2.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gissmann L., zur Hausen H. Partial characterization of viral DNA from human genital warts (Condylomata acuminata). Int J Cancer. 1980 May 15;25(5):605–609. doi: 10.1002/ijc.2910250509. [DOI] [PubMed] [Google Scholar]
  13. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  14. Kanda T., Furuno A., Yoshiike K. Human papillomavirus type 16 open reading frame E7 encodes a transforming gene for rat 3Y1 cells. J Virol. 1988 Feb;62(2):610–613. doi: 10.1128/jvi.62.2.610-613.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kanda T., Watanabe S., Yoshiike K. Immortalization of primary rat cells by human papillomavirus type 16 subgenomic DNA fragments controlled by the SV40 promoter. Virology. 1988 Jul;165(1):321–325. doi: 10.1016/0042-6822(88)90694-0. [DOI] [PubMed] [Google Scholar]
  16. Kaur P., McDougall J. K. Characterization of primary human keratinocytes transformed by human papillomavirus type 18. J Virol. 1988 Jun;62(6):1917–1924. doi: 10.1128/jvi.62.6.1917-1924.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lehn H., Villa L. L., Marziona F., Hilgarth M., Hillemans H. G., Sauer G. Physical state and biological activity of human papillomavirus genomes in precancerous lesions of the female genital tract. J Gen Virol. 1988 Jan;69(Pt 1):187–196. doi: 10.1099/0022-1317-69-1-187. [DOI] [PubMed] [Google Scholar]
  18. Lorincz A. T., Lancaster W. D., Temple G. F. Cloning and characterization of the DNA of a new human papillomavirus from a woman with dysplasia of the uterine cervix. J Virol. 1986 Apr;58(1):225–229. doi: 10.1128/jvi.58.1.225-229.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lorincz A. T., Temple G. F., Kurman R. J., Jenson A. B., Lancaster W. D. Oncogenic association of specific human papillomavirus types with cervical neoplasia. J Natl Cancer Inst. 1987 Oct;79(4):671–677. [PubMed] [Google Scholar]
  20. McCance D. J. Human papillomaviruses and cancer. Biochim Biophys Acta. 1986;823(3):195–205. doi: 10.1016/0304-419x(86)90002-8. [DOI] [PubMed] [Google Scholar]
  21. Morgan D., Pecoraro G., Rosenberg I., Defendi V. Transformation of C127 mouse fibroblasts by human papillomavirus 16. Cancer Res. 1988 May 1;48(9):2505–2511. [PubMed] [Google Scholar]
  22. Nuovo G. J., Crum C. P., De Villiers E. M., Levine R. U., Silverstein S. J. Isolation of a novel human papillomavirus (type 51) from a cervical condyloma. J Virol. 1988 Apr;62(4):1452–1455. doi: 10.1128/jvi.62.4.1452-1455.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pfister H. Human papillomaviruses and genital cancer. Adv Cancer Res. 1987;48:113–147. doi: 10.1016/s0065-230x(08)60691-0. [DOI] [PubMed] [Google Scholar]
  24. Pirisi L., Yasumoto S., Feller M., Doniger J., DiPaolo J. A. Transformation of human fibroblasts and keratinocytes with human papillomavirus type 16 DNA. J Virol. 1987 Apr;61(4):1061–1066. doi: 10.1128/jvi.61.4.1061-1066.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Potter H., Weir L., Leder P. Enhancer-dependent expression of human kappa immunoglobulin genes introduced into mouse pre-B lymphocytes by electroporation. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7161–7165. doi: 10.1073/pnas.81.22.7161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Reid R., Greenberg M., Jenson A. B., Husain M., Willett J., Daoud Y., Temple G., Stanhope C. R., Sherman A. I., Phibbs G. D. Sexually transmitted papillomaviral infections. I. The anatomic distribution and pathologic grade of neoplastic lesions associated with different viral types. Am J Obstet Gynecol. 1987 Jan;156(1):212–222. doi: 10.1016/0002-9378(87)90241-9. [DOI] [PubMed] [Google Scholar]
  27. Reiss M., Jastreboff M. M., Bertino J. R., Narayanan R. DNA-mediated gene transfer into epidermal cells using electroporation. Biochem Biophys Res Commun. 1986 May 29;137(1):244–249. doi: 10.1016/0006-291x(86)91202-7. [DOI] [PubMed] [Google Scholar]
  28. Schwarz E., Freese U. K., Gissmann L., Mayer W., Roggenbuck B., Stremlau A., zur Hausen H. Structure and transcription of human papillomavirus sequences in cervical carcinoma cells. Nature. 1985 Mar 7;314(6006):111–114. doi: 10.1038/314111a0. [DOI] [PubMed] [Google Scholar]
  29. Shirasawa H., Tomita Y., Kubota K., Kasai T., Sekiya S., Takamizawa H., Simizu B. Detection of human papillomavirus type 16 DNA and evidence for integration into the cell DNA in cervical dysplasia. J Gen Virol. 1986 Sep;67(Pt 9):2011–2015. doi: 10.1099/0022-1317-67-9-2011. [DOI] [PubMed] [Google Scholar]
  30. Stanley M. A., Parkinson E. K. Growth requirements of human cervical epithelial cells in culture. Int J Cancer. 1979 Oct 15;24(4):407–414. doi: 10.1002/ijc.2910240406. [DOI] [PubMed] [Google Scholar]
  31. Steinberg M. L., Defendi V. Altered pattern of growth and differentiation in human keratinocytes infected by simian virus 40. Proc Natl Acad Sci U S A. 1979 Feb;76(2):801–805. doi: 10.1073/pnas.76.2.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Storey A., Pim D., Murray A., Osborn K., Banks L., Crawford L. Comparison of the in vitro transforming activities of human papillomavirus types. EMBO J. 1988 Jun;7(6):1815–1820. doi: 10.1002/j.1460-2075.1988.tb03013.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Tase T., Okagaki T., Clark B. A., Manias D. A., Ostrow R. S., Twiggs L. B., Faras A. J. Human papillomavirus types and localization in adenocarcinoma and adenosquamous carcinoma of the uterine cervix: a study by in situ DNA hybridization. Cancer Res. 1988 Feb 15;48(4):993–998. [PubMed] [Google Scholar]
  34. Woodworth C. D., Bowden P. E., Doniger J., Pirisi L., Barnes W., Lancaster W. D., DiPaolo J. A. Characterization of normal human exocervical epithelial cells immortalized in vitro by papillomavirus types 16 and 18 DNA. Cancer Res. 1988 Aug 15;48(16):4620–4628. [PubMed] [Google Scholar]
  35. Yasumoto S., Burkhardt A. L., Doniger J., DiPaolo J. A. Human papillomavirus type 16 DNA-induced malignant transformation of NIH 3T3 cells. J Virol. 1986 Feb;57(2):572–577. doi: 10.1128/jvi.57.2.572-577.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. de Villiers E. M., Gissmann L., zur Hausen H. Molecular cloning of viral DNA from human genital warts. J Virol. 1981 Dec;40(3):932–935. doi: 10.1128/jvi.40.3.932-935.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES