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Distinct squamous phenotypes of human ectocervical cell lines immortalized by human papillomavirus type 16



Distinct squamous phenotypes of human ectocervical cell lines immortalized by human papillomavirus type 16



Molecular & Cellular Differentiation 2(2): 141-157



Compelling evidence indicates a role of particular human papillomaviruses (HPVs) in the etiology of cervical cancer. To study cervical cells as a model for the origin of and progression to these cancers, human ectocervical cells were transfected with HPV 16 DNA, immortalized cultures were established, and four clonal cell lines were selected. Each line contained differently integrated viral DNA. One line, HEC16-1, expressed distinct total viral RNA species and E7 antisense RNA. The four cell lines were nontumorigenic and formed differentiated lesions with a dysplastic change in implants under the skin of nude mice. However, the implants from each of the four cell lines were reconstructed into an epithelium that appeared to be unique. All of the four cell lines homogeneously expressed type I cytokeratins (CKs) 13 and 14, which are specific to ectocervical cells. Unique to the HEC 1 6-1 immortalized line, most of the cells expressed CK10/11 and did not express CK 19 or vimentin. Other unique characteristics were the cell line HEC16-2 homogeneous fibronectin expression, HEC 16-3 production of CK 18, and HEC 16-4 less-upregulated laminin expression. The results indicate that these HPV 16-immortalized cell lines had four distinct squamous epithelial phenotypes that are associated with differentiation and malignant potential. Moreover, CK10/11 and CK 18 expression was novel for ectocervical keratinocyte cell cultures. Therefore, the phenotypes of ectocervical cells are altered and possibly selected among by immortalization by HPV 16.

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