Effects of 17beta-estradiol and progesterone on transcription of human papillomavirus 16 E6/E7 oncogenes in CaSki and SiHa cell lines

Abstract

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.

Age-specific prevalence of HPV genotypes in cervical cytology samples with equivocal or low-grade lesions

“…Some evidence suggests a hormonal effect on oncogene expression, at least for HPV16 and 18, by action on progesterone/glucocorticoid-responsive elements in the long control region of the HPV genome (Cole and Danos, 1987;Gloss et al, 1989). However, more recent research has called such a mechanism into question (Ruutu et al, 2006), and would instead suggest hormonal effects impairing apoptosis of infected cells. Oral contraceptives and high parity are known risk factors for cervical cancer (Munoz et al, 2002).…”

Human Papillomavirus Infections in Nonsexually Active Perinatally HIV Infected Children

“…Both estrogen and progesterone have been shown to increase HPV replication and transcription, 18 thereby increasing viral load and making HPV easier to detect. Several studies have shown that it is difficult for most assays to detect low levels of HPV reliably.…”

Human papillomavirus, cervical carcinogenesis and chemoprevention with Indole derivates – a review of pathomechanisms

“…However, a study on HPV-16 positive CaSki and SiHa cells showed increased cell proliferation under the influence of oestrogen as well as progesterone but no change in HPV-16 E6/E7 transcription levels [50]. The authors suggested that the anti-apoptotic effect of oestrogen might allow a growth advantage for HPV infected cells [50]. In a model using luciferase reporter constructs under control of oestrogen response element promoter it was shown that HPV-16 E7 can dysregulate and reduce the function of steroid receptor coactivator 1, which may explain the role of steroid hormones as co-factors in the carcinogenesis of HR-HPV related disease [58].…”

“…HPV oncogene expression may be increased in response to oestrogen and progesterone stimulation, thus causing cell growth [49,[51][52][53][54][55][56][57]. However, a study on HPV-16 positive CaSki and SiHa cells showed increased cell proliferation under the influence of oestrogen as well as progesterone but no change in HPV-16 E6/E7 transcription levels [50]. The authors suggested that the anti-apoptotic effect of oestrogen might allow a growth advantage for HPV infected cells [50].…”

“…Oestrogen inhibits apoptosis in cervical cancer cells [49,50]. HPV oncogene expression may be increased in response to oestrogen and progesterone stimulation, thus causing cell growth [49,[51][52][53][54][55][56][57].…”