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Oestrogen and progesterone increase the levels of apoptosis induced by the human papillomavirus type 16 E2 and E7 proteins

Webster, Kenneth; Taylor, Anna; Gaston, Kevin

Authors

Kenneth Webster

Anna Taylor



Abstract

Human papillomavirus (HPV) type 16 infects the genital tract and is generally acknowledged to be a causative agent of cervical cancer. HPV infection alone is not sufficient to induce cervical cancer and other factors such as steroid hormones are thought to play a role in the establishment and/or progression of this disease. The HPV-16 E2 protein is required for virus replication and modulates viral gene expression whereas the HPV-16 E7 protein is required for cell transformation. We and others have shown that both the E2 and E7 proteins can induce apoptotic cell death in HPV-transformed and non-HPV transformed cell lines. Here we show that the steroid hormones oestrogen and progesterone can both increase the levels of E2- and E7-induced apoptosis. The oestrogen metabolite 16?-hydroxyoestrone also increases E2- and E7-induced cell death and the dietary component indole-3-carbinol, which reduces the formation of 16?-hydroxyoestrone from oestrogen, blocks the effects of oestrogen. Thus the metabolism of oestrogen to 16?-hydroxyoestrone appears to be required for the effects of this hormone on E2- and E7-induced cell death. We also show that the oestrogen receptor antagonist 3-hydroxytamoxifen blocks the effects of oestrogen on E2- and E7-induced cell death, whereas the anti-progesterone RU486 blocks the effects of both progesterone and oestrogen. We discuss these results in terms of the origin and progression of cervical cancer.

Citation

Webster, K., Taylor, A., & Gaston, K. (2001). Oestrogen and progesterone increase the levels of apoptosis induced by the human papillomavirus type 16 E2 and E7 proteins. Journal of General Virology, 82(1), 201-213. https://doi.org/10.1099/0022-1317-82-1-201

Journal Article Type Article
Acceptance Date Sep 26, 2000
Publication Date 2001-01
Deposit Date Nov 6, 2018
Journal Journal of General Virology
Print ISSN 0022-1317
Publisher Microbiology Society
Peer Reviewed Peer Reviewed
Volume 82
Issue 1
Pages 201-213
DOI https://doi.org/10.1099/0022-1317-82-1-201
Public URL https://nottingham-repository.worktribe.com/output/1037814
Publisher URL http://jgv.microbiologyresearch.org/content/journal/jgv/10.1099/0022-1317-82-1-201