1887

Abstract

CaSki cells are a human papillomavirus type 16 (HPV-16)-positive cell line that serves as a model for the study of advanced cervical carcinoma. Calcium is an important regulator of normal ectocervical epithelial cell differentiation. HPV E6 and E7 gene products are thought to be important in the process of cervical cell immortalization and hence important in the development of cervical cancer. In the present study we examine the relationship between CaSki cell differentiation and expression of the papillomavirus oncogenes. Shifting CaSki cells from medium containing low (0·06 m) to high (1·4 m) calcium results in an increase in cell-cell contact and increased differentiation as measured by an increase in the level of mRNA encoding cytokeratin K13, involucrin and type 1 transglutaminase, which are markers of differentiation in the cervical epithelium. In contrast, E6/E7 transcripts are produced in a differentiation-independent constitutive manner. These results and those from our previous experiments with HPV-16-immortalized but non-tumorigenic cell lines suggest that the constitutive, differentiation-independent expression of E6/E7 levels is a property of both tumorigenic and non-tumorigenic HPV-16-positive cancer cells.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-75-5-1139
1994-05-01
2022-01-24
Loading full text...

Full text loading...

/deliver/fulltext/jgv/75/5/JV0750051139.html?itemId=/content/journal/jgv/10.1099/0022-1317-75-5-1139&mimeType=html&fmt=ahah

References

  1. Agarwal C., Eckert R. L. 1990; Immortalization of human keratinocytes by simian virus 40 large T-antigen alters keratin gene response to retinoids. Cancer Research 50:5947–5953
    [Google Scholar]
  2. Agarwal C., Rorke E. A., Irwin J. C., Eckert R. L. 1991; Immortalization by human papillomavirus type 16 alters retinoid regulation of human ectocervical epithelial cell differentiation. Cancer Research 51:3982–3989
    [Google Scholar]
  3. Aviv H., Leder P. 1972; Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid cellulose. Proceedings of the National Academy of Sciences U.S.A: 691408–1412
    [Google Scholar]
  4. 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 sequences in cervical carcinoma cell lines. Journal of Virology 61:962–971
    [Google Scholar]
  5. Beaudenon S., Kremsdorf D., Croissant O., Jablonska S., Wain-Hobson S., Orth G. A. 1986; A novel type of human papillomavirus associated with genital neoplasias. Nature; London: 321246–249
    [Google Scholar]
  6. Berridge M. J. 1988; Inositol lipids and calcium signalling. Proceedings of the Royal Society of London (Biology) 234:359–378
    [Google Scholar]
  7. Boedtker H. 1971; Conformation independent molecular weight determination of RNA by gel electrophoresis. Biochimica et biophysica acta 240:448–453
    [Google Scholar]
  8. Boshart M., Gissmann L., Ikenberg H., Kleinheinz A., Scheur-Len 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 Journal 3:1151–1157
    [Google Scholar]
  9. Brennan J. K., Mansky J., Roberts G., Lichtman M. A. 1975; Improved methods for reducing calcium and magnesium concentration in tissue culture medium: applications to studies of lymphoblast proliferation in vitro. In Vitro 11:354–360
    [Google Scholar]
  10. Broker T. R. 1987; Structure and genetic expression of papillomaviruses. Obstetrics and Gynecology Clinics of North America 14:329–348
    [Google Scholar]
  11. Chan W. K., Klock G., Bernard H. U. 1989; Progesterone and glucocorticoid response elements occur in the long control regions of several human papillomaviruses involved in anogenital neoplasia. Journal of Virology 63:3261–3269
    [Google Scholar]
  12. Chan W. K., Chong T., Bernard H. U., Klock G. 1990; Transcription of the transforming genes of the oncogenic human papillomavirus-16 is stimulated by tumor promoters through API binding sites. Nucleic Acids Research 18:763–769
    [Google Scholar]
  13. Choo C. K., Rorke E. A., Eckert R. L. 1993; Calcium regulates the differentiation of human papillomavirus type 16 (HPV 16) immortalized epithelial cells, but not the expression of the papillomavirus E6 and E7 oncogenes. Experimental Cell Research 208:161–169
    [Google Scholar]
  14. Crum C. P., Nuovo G., Friedman D., Silverstein S. J. 1988; Accumulation of RNA homologous to human papillomavirus type 16 open reading frames in genital precancers. Journal of Virology 62:84–90
    [Google Scholar]
  15. Czernobilsky B., Moll R., Franke W. W., Dallenbach-Hell-Weg G., Hohlweg-Majert P. 1984; Intermediate filaments of normal and neoplastic tissues of the female genital tract with emphasis on problems of differential tumor diagnosis. Pathology Research and Practice 179:31–37
    [Google Scholar]
  16. Di Luca D., Pilotti S., Stefanon B., Rotola A., Monini P., Tognon M., De Palo G., Rilke F., Cassai E. 1986; Human papillomavirus type 16 DNA in genital tumours: a pathological and molecular analysis. Journal of General Virology 67:583–589
    [Google Scholar]
  17. Dixon I. S., Stanley M. A. 1984; Immunofluorescent studies of human cervical epithelia in vivo and in vitro using antibodies against specific keratin components. Molecular Biology and Medicine 2:37–51
    [Google Scholar]
  18. Durst M., Gissmann L., Ikenberg H., Zur Hausen H. 1983; A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proceedings of the National Academy of Sciences U.S.A: 803812–3815
    [Google Scholar]
  19. Durst 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]
  20. Eckert R. L. 1989; Structure, function and differentiation of the keratinocyte. Physiological Reviews 69:1316–1346
    [Google Scholar]
  21. Eckert R. L., Green H. 1984; Cloning of cDNAs specifying vitamin A-responsive human keratins. Proceedings of the National Academy of Sciences U.S.A: 814321–4325
    [Google Scholar]
  22. Eckert R. L., Green H. 1986; Structure and evolution of the human involucrin gene. Cell 46:583–589
    [Google Scholar]
  23. Floyd E. D., Jetten A. M. 1989; Regulation of type I (epidermal) transglutaminase mRNA levels during squamous differentiation: down regulation by retinoids. Molecular and Cellular Biology 9:4846–4851
    [Google Scholar]
  24. Forslind B., Roomans G. M., Carlsson L. E., Malmqvist K. G., Akselsson K. R. 1984; Elemental analysis on freeze-dried sections of human skin: studies by electron microscope and particle induced X-ray emission analysis. Scanning Electron Microscopy 11:755–759
    [Google Scholar]
  25. Gentile B., Thomazy V., Piacentini M., Fesus L., Davies P. J. 1992; Expression of tissue transglutaminase in Balb-C 3T3 fibroblasts: effects on cellular morphology and adhesion. Journal of Cell Biology 119:463–474
    [Google Scholar]
  26. Gilfix B. M., Eckert R. L. 1985; Coordinate control by vitamin A of keratin gene expression in human keratinocytes. Journal of Biological Chemistry 260:14026–14029
    [Google Scholar]
  27. Gloss B., Bernard H. U., Seedorf K., Klock G. 1987; The upstream regulatory region of the human papillomavirus-16 contains an E2 protein-independent enhancer which is specific for cervical carcinoma cells and regulated by glucocorticoids. EMBO Journal 6:3735–3743
    [Google Scholar]
  28. Gorodeski G. I., Eckert R. L., Utian W. H., Sheean L., Rorke E. A. 1989; Retinoids, sex steroids and glucocorticoids regulate ectocervical cell envelope formation but not the level of the envelope precursor, involucrin. Differentiation 42:75–80
    [Google Scholar]
  29. Gorodeski G. I., Eckert R. L., Utian W. H., Rorke E. A. 1990a; Maintenance of in vivo-like keratin expression, sex steroid responsiveness, and estrogen receptor expression in cultured human ectocervical epithelial cells. Endocrinology 126:399–406
    [Google Scholar]
  30. Gorodeski G. I., Eckert R. L., Utian W. H., Sheean L., Rorke E. A. 1990b; Cultured human ectocervical epithelial cell differentiation is regulated by the combined direct actions of sex steroids, glucocorticoids and retinoids. Journal of Clinical Endocrinology and Metabolism 70:1624–1630
    [Google Scholar]
  31. Gorodeski G. I., Romero M. F., Hopfer U., Rorke E. A., Utian W. H., Eckert R. L. 1994; Human uterine cervical epithelial cells grown on permeable support - a new model for the study of differentiation. Differentiation in press
    [Google Scholar]
  32. Heenen M., Graef C. D., Galand P. 1992; Kinetics of the calcium induced stratification of human keratinocytes in vitro. Cell Proliferation 25:233–240
    [Google Scholar]
  33. Hennings H., Michael D., Cheng C., Steinert P., Holbrook K., Yuspa S. H. 1980; Calcium regulation of growth and differentiation of mouse epidermal cells in culture. Cell 19:245–254
    [Google Scholar]
  34. Herrington C. S., Burns J., Graham A. K., Evans M., Mcgee J. O. 1989; Interphase cytogenetics using biotin and digoxigenin labelled probes I: relative sensitivity of both reporter molecules for detection of HPV16 in CaSki cells. Journal of Clinical Pathology 42:592–600
    [Google Scholar]
  35. Hirochika H., Hirochika R., Broker T. R., Chow L. T. 1988; Functional mapping of the human papillomavirus type 11 transcriptional enhancer and its interaction with the transacting E2 proteins. Genes and Development 2:54–67
    [Google Scholar]
  36. Hummel M., Hudson J. B., Laimins L. A. 1992; Differentiation- induced and constitutive transcription of human papillomavirus type 31b in cell lines containing viral episomes. Journal of Virology 66:6070–6080
    [Google Scholar]
  37. Iftner T., Oft M., Bohm S., Wilczynski S. P., Pfister H. 1992; Transcription of the E6 and E7 genes of human papillomavirus type 6 in anogenital condylomata is restricted to the undifferentiated cell layers of the epithelium. Journal of Virology 66:4639–1646
    [Google Scholar]
  38. Jaken S., Yuspa S. H. 1988; Early signals for keratinocytes differentiation: role of Ca2+-mediated inositol lipid metabolism in normal and neoplastic epidermal cells. Carcinogenesis 9:1033–1038
    [Google Scholar]
  39. Jeng A. Y., Lichti U., Strickland J. E., Blumberg P. M. 1985; Similar effects of phospholipase C and phorbol ester tumor promoters on primary mouse epidermal cells. Cancer Research 45:5714–5721
    [Google Scholar]
  40. Kasturi L., Sizemore N., Eckert R. L., Martin K., Rorke E. A. 1993; Calcium regulates cornified envelope formation, involu- crin content and transglutaminase activity in cultured human ectocervical epithelial cells. Experimental Cell Research 205:84–90
    [Google Scholar]
  41. Lettvin J. Y., Pickard W. F., Mcculloch W. S., Pitts W. 1964; A theory of passive ion flux through membrane. Nature; London: 2021338–1339
    [Google Scholar]
  42. Levy R., Czernobilsky B., Geiger B. 1988; Subtyping of epithelial cells of normal and metaplastic human uterine cervix, using polypeptide-specific cytokeratin antibodies. Differentiation 39:185–196
    [Google Scholar]
  43. Malmqvist K. G., Carlsson L. E., Forslind B., Roomans G. M., Akselsson K. R. 1984; Proton and electron microprobe analysis of human skin. Nuclear Instruments and Methods in Physics Research B 3:611–617
    [Google Scholar]
  44. Mauro T. M., Isseroff R. R., Lasarow R., Pappone P. A. 1993; Ion channels are linked to differentiation in keratinocytes. Journal of Membrane Biology 132:201–209
    [Google Scholar]
  45. Menon G. K., Grayson S., Elias P. M. 1985; Ionic calcium reservoirs in mammalian epidermis: ultrastructural localization by ion-capture cytochemistry. Journal of Investigative Dermatology 84:508–512
    [Google Scholar]
  46. Moll R., Franke W. W., Schiller D. L., Geiger B., Drepler R. 1982; The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell 31:11–24
    [Google Scholar]
  47. Moll R., Levy R., Czernobilsky B., Hohlweg-Majert P., Dallenbach-Hellweg G., Franke W. W. 1983; Cytokeratins of normal epithelia and some neoplasms of the female genital tract. Laboratory Investigation 49:599–610
    [Google Scholar]
  48. Moscat J., Fleming T. P., Molloy C. J., Lopez-Barahona M., Aaronson S. A. 1989; The calcium signal for Balb/Mk keratino- cyte terminal differentiation induces sustained alteration in phospho- inositide metabolism without detectable protein kinase C activation. Journal of Biological Chemistry 264:11228–11235
    [Google Scholar]
  49. Munger K., Phelps W. C., Bubb V., Howley P. M., 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. Journal of Virology 63:4417–4421
    [Google Scholar]
  50. O’Farrell P. Z., Goodman H. M., O’Farrell P. H. 1977; High resolution two-dimensional electrophoresis of basic as well as acidic proteins. Cell 12:1133–1141
    [Google Scholar]
  51. Pattillo R. A., Hussa R. O., Story M. T., Ruckert A. C. F., Shalaby M. R., Mattingly R. F. 1977; Tumor antigen and human chorionic gonadotropin in CaSki cells: a new epidermoid cervical cancer cell line. Science 196:1456–1458
    [Google Scholar]
  52. Pillai S., Bikle D. D. 1992; Lanthanum influx into cultured human keratinocytes: effect on calcium flux and tenninal differentiation. Journal of Cellular Physiology 151:623–629
    [Google Scholar]
  53. Pillai S., Bikle D. D., Mancianti M. L., Cline P., Hincenbergs M. 1990; Calcium regulation of growth and differentiation of normal human keratinocytes: modulation of differentiation competence by stage of growth and extracellular calcium. Journal of Cellular Physiology 143:294–302
    [Google Scholar]
  54. Pirisi L., Yasumoto S., Feller M., Doniger 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]
  55. Rice R. H., Green H. 1979; Presence in human epidermal cells of a soluble protein precursor of the cross-linked envelope: activation of the cross-linking by calcium ions. Cell 18:681–694
    [Google Scholar]
  56. Rothblat G. H., Arbogast L. Y., Quellett L., Howard B. V. 1976; Preparation of delipidized serum protein for use in cell culture systems. In Vitro 12:554–557
    [Google Scholar]
  57. Rothnagel J. A., Mehrel T., Idler W. W., Roop D. R., Steinert P. M. 1987; The gene for mouse epidermal filaggrin precursor. Its partial characterization, expression and sequence of a repeating filaggrin unit. Journal of Biological Chemistry 262:15643–15648
    [Google Scholar]
  58. Rubin A. L., Rice R. H. 1986; Differential regulation by retinoic acid and calcium of transglutaminases in cultured neoplastic and normal keratinocytes. Cancer Research 46:2356–2361
    [Google Scholar]
  59. Rubin A. L., Rice R. H. 1988; Characterization of the calcium sensitivity of differentiation in SCC-13 human squamous carcinoma cells. In Vitro Cellular and Developmental Biology 24:857–861
    [Google Scholar]
  60. Seedorf K., Krammer G., Durst M., Suhai S., Rowekamp W. G. 1985; Human papillomavirus type 16 DNA sequence. Virology 145:181–185
    [Google Scholar]
  61. Sharpe G. R., Fisher C., Gillespie J. I., Greenwell J. R. 1933; Growth and differentiation stimuli induce different and distinct increases in intracellular free calcium in human keratinocytes. Archives of Dermatological Research 284:445–150
    [Google Scholar]
  62. Sizemore N., Kasturi L., Gorodeski G., Eckert R. L., Jetten A. M., Rorke E. A. 1993; Retinoid regulation of human ectocervical epithelial cell transglutaminase activity and keratin gene expression. Differentiation 54:219–225
    [Google Scholar]
  63. Smedts R., Ramaekers F., Robben H., Pruszczynski M., Vanmuijen G., Lane B., Leigh I., Vooijs P. 1990; Changing patterns of keratin expression during progression of cervical intraepithelial neoplasia. American Journal of Pathology 136:657–668
    [Google Scholar]
  64. Stoler M. H., Broker T. R. 1986; In situ hybridization detection of human papillomavirus DNAs and messenger RNAs in genital condylomas and a cervical carcinoma. Human Pathology 17:1250–1258
    [Google Scholar]
  65. Stoler M. H., Rhodes C. R., Whitbeck A., Chow L. T., Broker T. R. 1990; Gene expression of HPV types 16 and 18 in cervical neoplasia. In Papillomaviruses pp 1–11 Howley P. M., Broker T. R. Edited by New York: Wiley-Liss;
    [Google Scholar]
  66. Sun T. -T., Tseng S. C., Huang A. J. -W., Cooper D., Schermer A., Lynch M. H., Weiss R., Eichner R. 1985; Monoclonal antibody studies of mammalian epithelial keratins: a review. Annals of the New York Academy of Sciences 455:307–329
    [Google Scholar]
  67. Swift F. V., Bhat K., Younghusband H. B., Hamada H. 1987; Characterization of a cell type-specific enhancer found in the human papilloma virus type 18 genome. EMBO Journal 6:1339–1344
    [Google Scholar]
  68. Tang W., Ziboh V. A., Isseroff R., Martinez D. 1988; Turnover of inositol phospholipids in cultured murine keratinocytes: possible involvement of inositol triphosphate in cellular differentiation. Journal of Investigative Dermatology 90:37–43
    [Google Scholar]
  69. Van Breeman C., Aaronson P., Loutzenhiser R. 1979; Sodium- calcium interactions in mammalian smooth muscle. Pharmacological Reviews 30:167–208
    [Google Scholar]
  70. Watt F. M., Green H. 1982; Stratification and terminal differentiation of cultured epidermal cells. Nature; London: 295434–436
    [Google Scholar]
  71. Weikel W., Wagner R., Moll R. 1987; Characterization of subcolumnar reserve cells and other epithelia of human uterine cervix. Virchows Archiv B Cell Pathology 54:98–110
    [Google Scholar]
  72. Weiss G. B. 1974; Cellular pharmacology of lanthanum. Annual Review of Pharmacology 14:343–354
    [Google Scholar]
  73. Woodworth C. D., Doniger 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]
  74. Yee C., Krishnan-Hewlett I., Baker C. C., Schlegel R., Howley P. M. 1985; Presence and expression of human papillomavirus sequences in human cervical carcinoma cell lines. American Journal of Pathology 119:361–366
    [Google Scholar]
  75. Yuspa S, Ben T., Henning H., Lichti U. 1980; Phorbol ester tumor promoters induce epidermal transglutaminase activity. Biochemical and Biophysical Research Communications 97:700–708
    [Google Scholar]
  76. Yuspa S. H., Ben T., Henning H., Lichti U. 1982; Divergent responses in epidermal basal cells exposed to the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate. Cancer Research 42:2344–2349
    [Google Scholar]
  77. Yuspa S. H., Kilkenny A. E., Steinert P. M., Roop D. R. 1989; Expression of murine epidermal differentiation markers is tightly regulated by restricted extracellular calcium concentrations in vitro. Journal of Cell Biology 109:1207–1217
    [Google Scholar]
  78. Zur Hausen H. 1977; Human papillomaviruses and their possible role in squamous cell carcinomas. Current Topics in Microbiology and Immunology 78:1–30
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-75-5-1139
Loading
/content/journal/jgv/10.1099/0022-1317-75-5-1139
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