Effects of 17beta-estradiol and progesterone on transcription of human papillomavirus 16 E6/E7 oncogenes in CaSki and SiHa cell lines.
Several in vitro studies have addressed the interactions between estrogen/progesterone and human papillomavirus (HPV), but the results are controversial. We evaluated the effects of estrogen and progesterone and their antagonists on messenger RNA expression of HPV16 E6/E7 in HPV16-positive cell lines CaSki and SiHa with real-time reverse-transciptase polymerase chain reaction method. Colorimetric assay with tetrazolium salt (WST-1) and flow cytometry were used for testing proliferation and apoptosis. No statistically significant changes were found after hormone treatment in the expression of HPV16 E6/E7 or hormone receptors in CaSki and SiHa cell lines. Progesterone increased cell proliferation in both the cells, while estrogen increased proliferation of SiHa cells only. Estrogen seemed to protect the CaSki cells from apoptosis, and tamoxifen did not abrogate this effect. Progesterone slightly increased apoptosis of CaSki cells, and this effect was neutralized with RU486. In this study, estrogen and progesterone did not change either the transcription levels of HPV16 E6/E7 or estrogen receptor or progesterone receptor levels. Hormone receptor antagonists had no effect on transcription. Both hormones might have a permissive effect for the growth of cervical cancer, by promoting cell proliferation and making the cells vulnerable to mutations. In addition, estrogen acts as an antiapoptotic agent allowing growth advance of the cells infected with oncogenic HPV.
Ruutu
M
M
Department of Oral Pathology and Oral Radiology, Institute of Dentistry and MediCity Research Laboratory, Faculty of Medicine, University of Turku, Lemminkäisenkatu 2, FIN-20520 Turku, Finland. merja.ruutu@utu.fi
Wahlroos
N
N
Syrjänen
K
K
Johansson
B
B
Syrjänen
S
S
D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured
C068651:E6 protein, Human papillomavirus type 16; D004965:Estrogen Antagonists; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011960:Receptors, Estrogen; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D013629:Tamoxifen; D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol