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Differentiation-independent Constitutive Expression of the Human Papillomavirus Type 16 E6 and E7 Oncogenes in the CaSki Cervical Tumour Cell Line

¹ Department of Physiology and Biophysics,
² Department of Reproductive Biology,
³ Department of Dermatology,
⁴ Department of Environmental Health Sciences
and⁵ Department of Biochemistry, Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, Ohio 44106-4970, U.S.A.

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 mM) to high (1.4 mM) 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.

Received 20 August 1993; accepted 9 December 1993.

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