Altered growth behavior of human cervical epithelial cells transfected by HPV type 16 and 18 DNA

Transfection of primary human cervical epithelial (HCE) cells with full-length HPV type 16 and 18 DNAs resulted in cell lines that could grow continuously. Four HPV DNA-immortalized cell lines were established. Morphologically the immortalized cells resembled primary HCE cells. Electron microscopy showed that they contained desmosomes and keratin filaments, which are characteristic structural components of epithelial cells. Each cell line had a unique integration pattern of HPV DNA but the transcription patterns were similar in the 3 HPV 16 DNA-immortalized cell lines. The expression patterns of viral DNA in the HPV 18 DNA-immortalized cell line were similar to that in HeLa cells, suggesting transcription of mainly early viral genes. The cell lines, unlike HeLa and SiHa carcinoma cells, did not form tumors in nude mice or grow in soft agarose, but collagen raft culture indicated that the immortalized cell lines had lost the capacity of normal differentiation compared with primary HCE cells. Morphologically, the aberrant differentiation of the immortalized cells showed great resemblance to cervical intra-epithelial neoplasia. The altered pattern of growth and differentiation of human cervical epithelial cells transfected by HPV 16 and 18 DNAs is in agreement with the view that HPV types 16 and 18 play an important role at an initial step of human cervical epithelial carcinogenesis but that co-carcinogenic factors are necessary for full malignant transformation in vivo.