Altered growth and viral gene expression in human papillomavirus type 16-containing cancer cell lines treated with progesterone.

This study explores interactions between high-risk human papillomavirus type 16 (HPV-16) and the female sex hormone progesterone in the growth of tumor cells and viral oncogene expression. For both the cervical cancer cell line CaSki containing integrated HPV-16 DNA and the laryngeal carcinoma cell line HEp-2 transfected with HPV-16 DNA, prolonged progesterone treatment enhances their colony formation efficiency both on plastic surface and in soft agar. In contrast, progesterone has no effect on the HPV-negative cervical cancer cell line C-33A or the untransfected HEp-2 parental cells. Progesterone increases HPV-16 E6/E7 oncogene transcription in both HPV-16-containing cell lines. A detectable increase requires at least 3 days of treatment, and this delayed response may be due, at least in part, to increased stability of viral transcripts as determined by actinomycin D treatment. The progesterone antagonist RU 486 and nuclease-resistant oligomers containing HPV-16 progesterone response element are able to abrogate the enhancement by progesterone on cell growth and E6/E7 gene transcription. Taken together, these results support the notion that progesterone can be a cofactor in HPV-related malignancies.