1887

Abstract

Human papillomavirus type 16 (HPV-16) transcription was analysed in one squamous cervical carcinoma by cDNA cloning and DNA sequencing, and in eight additional squamous cervical carcinomas and 11 precancerous lesions by RNA-RNA hybridization. The nucleotide sequences of the cDNA clones revealed structures of early HPV-16 mRNAs (E6*-E7-E1^E4-E5) in agreement with data reported for other premalignant and malignant tumours. cDNA clones possibly representing viral RNA of antisense orientation were also detected. These RNAs included sequences of the upstream regulatory region, part of the early and the late region of the genome. In three of eight squamous cervical carcinomas examined by hybridization, signals specific for viral antisense RNA were also found. The antisense RNAs had a predominantly nuclear localization. Viral antisense RNA could not be detected in any of 11 HPV-16-positive premalignant lesions. The expression of HPV antisense RNA is likely to be linked to viral integration into the host genome. The possible effects of viral antisense transcription with regard to tumour progression remain to be determined.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-73-7-1833
1992-07-01
2021-10-17
Loading full text...

Full text loading...

/deliver/fulltext/jgv/73/7/JV0730071833.html?itemId=/content/journal/jgv/10.1099/0022-1317-73-7-1833&mimeType=html&fmt=ahah

References

  1. Baker C. C., Phelps W. C., Lindgren V., Braun M. J., Gonda M. A., Howley P. M. 1987; Structural and transcriptional analysis of human papillomavirus type 16 in cervical carcinoma cell lines. Journal of Virology 61962–971
    [Google Scholar]
  2. Barbosa M. S., Edmonds C., Fisher C., Schiller J. T., Lowy D. R., Vousden K. H. 1990; The region of the HPV 16 E7 oncoprotein homologous to adenovirus Ela and SV40 large T antigen contains separate domains for Rb binding and casein kinase II phosphorylation. EMBO Journal 9:153–160
    [Google Scholar]
  3. Barbosa M. S., Vass W. C., Lowy D. R., Schiller J. T. 1991; In vitro biological activities of the E6 and E7 genes vary among human papillomaviruses of different oncogenic potential. Journal of Virology 65:292–298
    [Google Scholar]
  4. Bedell M. A., Hudson J. B., Golub T. R., Turyk M. E., Hosken M., Wilbanks G. D., Laimins L. A. 1991; Amplification of human papillomavirus genomes in vitro is dependent on epithelial differentiation. Journal of Virology 65:2254–2260
    [Google Scholar]
  5. Bubb V., McCance D. J., Schlegel R. 1988; DNA sequences of the HPV 16 E5 ORF and the structural conservation of its encoded protein. Virology 163:234–246
    [Google Scholar]
  6. Cornelissen M. T. E., Smits H. L., Briët M. A., van den Tweel J. G., Struyk A. P. H. B., van der Noordaa J., ter Schegget J. 1990; Uniformity of the splicing pattern of the E6/E7 transcripts in human papillomavirus type 16-transformed human fibroblasts, human cervical premalignant lesions and carcinomas. Journal of General Virology 71:1243–1246
    [Google Scholar]
  7. Crum C. P., Nuovo G., Friedman D., Silverstein S. J. 1988; Accumulation of RNA homologous to the human papillomavirus type 16 open reading frames in genital precancers. Journal of Virology 62:84–90
    [Google Scholar]
  8. Crum C. P., Barbar S., Symbula M., Snyders K., Saleh A. M., Roche J. K. 1990; Coexpression of the human papillomavirus type 16 E4 and LI open reading frames in early cervical neoplasias. Virology 178:238–246
    [Google Scholar]
  9. Cullen A. P., Reid R., Campion M., Lorincz A. T. 1991; Analysis of the physical state of different human papillomavirus DNAs in intraepithelial and invasive cervical neoplasm. Journal of Virology 65:606–612
    [Google Scholar]
  10. Dilts D. P., Broker T. R., Chow L. T. 1990; The structures of the human papillomavirus type 1 and type 16 messenger RNAs determined by polymerase chain reaction. In Papillomaviruses pp 533–540 Edited by Howley P. M., Broker T. R. New York: Wiley-Liss;
    [Google Scholar]
  11. Doorbar J., Parton A., Hartley K., Banks L., Crook T., Stanley M., Crawford L. 1990; Detection of novel splicing patterns in a HPV 16-containing keratinocyte cell line. Virology 178:254–262
    [Google Scholar]
  12. Dürst M., Kleinheinz A., Hotz M., Gissmann L. 1985; The physical state of human papillomavirus type 16 DNA in benign and malignant genital tumours. Journal of General Virology 66:1515–1522
    [Google Scholar]
  13. Dürst M., Dzarlieva-Petrusevska R. T., Boukamp P., Fusenig N. E., 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
    [Google Scholar]
  14. Dürst M., Bosch F. X., Glitz D., Schneider A., zur Hausen H. 1991; Inverse relationship between human papillomavirus (HPV) type 16 early gene expression and cell differentiation in nude mouse epithelial cysts and tumors induced by HPV-positive human cell lines. Journal of Virology 65:796–804
    [Google Scholar]
  15. Dyson N., Howley P. M., Münger K., Harlow E. 1989; The human papilloma virus-16 oncoprotein is able to bind to the retinoblastoma gene product. Science 243:934–937
    [Google Scholar]
  16. Gage J. R., Meyers C., Wettstein F. O. 1990; The E7 proteins of the nononcogenic human papillomavirus type 6b (HPV-6b) and of the oncogenic HPV-16 differ in retinoblastoma protein binding properties. Journal of Virology 64:723–730
    [Google Scholar]
  17. Halbert C. L., Galloway D. A. 1988; Identification of the E5 open reading frame of human papillomavirus type 16. Journal of Virology 62:1071–1075
    [Google Scholar]
  18. Hawley-Nelson P., Vousden K. H., Hubbert N. L., Lowy D. R., Schiller J. T. 1989; Human papillomavirus type 16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes. EMBO Journal 8:3905–3910
    [Google Scholar]
  19. Hélène C., Toulmé J. -J. 1990; Specific regulation of gene expression by anti-sense, sense and antigene nucleic acids. Biochimica et biophysica acta 1049:99–125
    [Google Scholar]
  20. Higgins G. D., Uzelin D. M., Phillips G. E., Burrell C. J. 1991; Presence and distribution of human papillomavirus sense and antisense RNA transcripts in genital cancers. Journal of General Virology 72:885–895
    [Google Scholar]
  21. Johnson M. A., Blomfield P. I., Bevan I. S., Woodman C. B. J., Young L. S. 1990; Analysis of human papillomavirus type 16 E6-E7 transcription in cervical carcinomas and normal cervical epithelium using the polymerase chain reaction. Journal of General Virology 71:1473–1479
    [Google Scholar]
  22. Matsukura T., Kanda T., Furuno A., Yoshikawa H., Kawana T., Yoshiike K. 1986; Cloning of monomeric human papillomavirus type 16 DNA integrated within cell DNA from a cervical carcinoma. Journal of Virology 58:979–982
    [Google Scholar]
  23. Münger K., Phelps W. C., Bubb V., Howley P. M., Schlegel R. 1989a; The E6 and E7 genes of the human papillomavirus type 16 together are necessary and sufficient for transformation of primary human keratinocytes. Journal of Virology 63:4417–4422
    [Google Scholar]
  24. Münger K., Werness B. A., Dyson N., Phelps W. C., Harlow E., Howley P. M. 1989b; Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product. EMBO Journal 8:4099–4105
    [Google Scholar]
  25. Parton A. 1990; Nucleotide sequence of the HPV 16 LI open reading frame. Nucleic Acids Research 18:3631
    [Google Scholar]
  26. Pecoraro G., Morgan D., Defendi V. 1989; Differential effects of human papillomavirus type 6, 16 and 18 DNAs on immortalization and transformation of human cervical epithelial cells. Proceedings of the National Academy of Sciences, U.S.A. 86:563–567
    [Google Scholar]
  27. Pirisi L., Yasumoto S., Feller M., Doninger J., DiPaolo J. A. 1987; Transformation of human fibroblasts and keratinocytes with human papillomavirus type 16 DNA. Journal of Virology 61:1061–1066
    [Google Scholar]
  28. Rohlfs M., Winkenbach S., Meyer S., Rupp T., Durst M. 1991; Viral transcription in human keratinocyte cell lines immortalized by human papillomavirus type 16. Virology 183:331–342
    [Google Scholar]
  29. Romanczuk H., Thierry F., Howley P. M. 1990; Mutational analysis of cis elements involved in E2 modulation of human papillomavirus type 16 P97 and type 18 P105 promoters. Journal of Virology 64:2849–2859
    [Google Scholar]
  30. Sambrook J., Fritsch E. F., Maniatis T. 1989 Molecular Cloning: A Laboratory Manual 2nd edn New York: Cold Spring Harbor Laboratory;
    [Google Scholar]
  31. Sanger F., Nicklen S., Coulson A. R. 1977; DNA sequencing with chain-terminating inhibitors. Proceedings of the National Academy of Sciences, U.S.A. 74:5463–5467
    [Google Scholar]
  32. Schlegel R., Phelps W. C., Zhang Y.-L., Barbosa M. 1988; Quantitative keratinocyte assay detects two biological activities of human papillomavirus DNA and identifies viral types associated with cervical carcinoma. EMBO Journal 7:3181–3187
    [Google Scholar]
  33. Schneider-Gädicke A., Schwarz E. 1986; Different human cervical carcinoma cell lines show similar transcription patterns of human papillomavirus type 18 early genes. EMBO Journal 5:2285–2292
    [Google Scholar]
  34. Schneider-Maunoury S., Pehau-Arnaudet G., Breitburd F., Orth G. 1990; Expression of the human papillomavirus type 16 genome in SK-v cells, a line derived from a vulvar intraepithelial neoplasia. Journal of General Virology 71:809–817
    [Google Scholar]
  35. Schwarz E., Freese U. K., Gissmann L., Mayer W., Roggen-buck B., Stremlau A., zur Hausen H. 1985; Structure and transcription of human papillomavirus sequences in cervical carcinoma cells. Nature, London 314:111–114
    [Google Scholar]
  36. Seedorf K., Krämmer G., Durst M., Suhai S., Rowekamp W. G. 1985; Human papillomavirus type 16 DNA sequence. Virology 145:181–185
    [Google Scholar]
  37. Sherman L., Golan I., Alloul N., Dürst M., Baram A. 1992; Expression and splicing pattern of human papillomavirus type 16 mRNAs in preinvasive and invasive carcinomas of the cervix, in human keratinocytes immortalized by HPV 16, and in cell lines established from cervical cancers. International Journal of Cancer 50:356–364
    [Google Scholar]
  38. Shirasawa H., Tomita Y., Kubota K., Kasai T., Sekiya S., Takamizawa H., Simizu B. 1988; Transcriptional differences of the human papillomavirus type 16 genome between precancerous lesions and invasive carcinomas. Journal of Virology 62:1022–1027
    [Google Scholar]
  39. Smotkin D., Wettstein F. O. 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. Proceedings of the National Academy of Sciences, U.S.A. 83:4680–4684
    [Google Scholar]
  40. Smotkin D., Prokoph H., Wettstein F. O. 1989; Oncogenic and nononcogenic human genital papillomaviruses generate the E7 mRNA by different mechanisms. Journal of Virology 63:1441–1447
    [Google Scholar]
  41. Spalholz B. A., Lambert P. F., Yee C. L., Howley P. M. 1987; Bovine papillomavirus transcriptional regulation: localization of the E2-responsive elements in the long control region. Journal of Virology 61:2128–2137
    [Google Scholar]
  42. Stoler M. H., Rhodes C. R., Whitbeck A., Chow L. T., Broker T. R. 1990; Gene expression of HPV 16 and 18 in cervical neoplasia. In Papillomaviruses pp 1–11 Edited by Howley P. M., Broker T. R. New York: Wiley-Liss;
    [Google Scholar]
  43. Takayama K. M., Inouye M. 1990; Antisense RNA. CRC Critical Reviews in Biochemistry and Molecular Biology 25:155–184
    [Google Scholar]
  44. von Knebel-Doeberitz M., Oltersdorf T., Schwarz E., Gissmann L. 1988; Correlation of modified human papillomavirus early gene expression with altered cell growth in C4–1 cervical cancer cells. Cancer Research 48:3780–3786
    [Google Scholar]
  45. von Knebel-Doeberitz M., Rittmuller C., zur Hausen H., Dürst M. 1992; Inhibition of tumorigenicity of cervical cancer cells in nude mice by HPV E6-E7 antisense RNA. International Journal of Cancer (in press)
    [Google Scholar]
  46. Watanabe S., Kanda T., Yoshiika K. 1989; Human papillomavirus type 16 transformation of primary human embryonic fibroblasts requires expression of open reading frames E6 and E7. Journal of Virology 63:965–969
    [Google Scholar]
  47. Werness B. A., Levine A. J., Howley P. M. 1990; Association of human papillomavirus type 16 and 18 E6 proteins with p53. Science 248:76–79
    [Google Scholar]
  48. Woodworth C. D., Doninger J., DiPaolo J. A. 1989; Immortalization of human foreskin keratinocytes by various human papillomavirus DNAs corresponds to their association with cervical carcinoma. Journal of Virology 63:159–164
    [Google Scholar]
  49. zur Hausen H. 1989; Papillomaviruses as carcinomaviruses. Advances in Viral Oncology 81–26
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-73-7-1833
Loading
/content/journal/jgv/10.1099/0022-1317-73-7-1833
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error