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.
Yuan
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F
Department of Biomedical Sciences, College of Osteopathic Medicine, Ohio University, Athens, USA.
Auborn
K
K
James
C
C
D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000821:virology; D002455:Cell Division / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D007822:Laryngeal Neoplasms / Q000473:pathology* / Q000821:virology; D015735:Mifepristone / Q000494:pharmacology; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins; D012260:Ribonucleases / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000821:virology; D014410:Tumor Stem Cell Assay; D002583:Uterine Cervical Neoplasms / Q000473:pathology* / Q000821:virology
C068651:E6 protein, Human papillomavirus type 16; D006727:Hormone Antagonists; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012367:RNA, Viral; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D003609:Dactinomycin; D015735:Mifepristone; D011374:Progesterone; D012260:Ribonucleases