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

Cancer Invest. 1999;17(1):19-29.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / virology
  • Cell Division / drug effects
  • Dactinomycin / pharmacology
  • Epithelial Cells / drug effects
  • Epithelial Cells / pathology
  • Female
  • Gene Expression Regulation, Viral / drug effects*
  • Hormone Antagonists / pharmacology
  • Humans
  • Laryngeal Neoplasms / pathology*
  • Laryngeal Neoplasms / virology
  • Mifepristone / pharmacology
  • Oncogene Proteins, Viral / biosynthesis
  • Oncogene Proteins, Viral / genetics
  • Papillomaviridae / genetics*
  • Papillomavirus E7 Proteins
  • Progesterone / antagonists & inhibitors
  • Progesterone / pharmacology*
  • RNA, Viral / biosynthesis
  • RNA, Viral / genetics
  • Repressor Proteins*
  • Ribonucleases / metabolism
  • Transcription, Genetic / drug effects
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / virology
  • Tumor Stem Cell Assay
  • Uterine Cervical Neoplasms / pathology*
  • Uterine Cervical Neoplasms / virology

Substances

  • E6 protein, Human papillomavirus type 16
  • Hormone Antagonists
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • RNA, Viral
  • Repressor Proteins
  • oncogene protein E7, Human papillomavirus type 16
  • Dactinomycin
  • Mifepristone
  • Progesterone
  • Ribonucleases