Abstract #2381: The role of the estrogen receptor on cervical cancer proliferation
Authors: Michelle Bonneau, Kirsty Cleverly, Michael Birrer, T. Wu, John Farley
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Objective: While it is now accepted that human papilloma virus (HPV) infection plays a vital role in cervical cancer carcinogenesis, the molecular mechanism of infection remains to be elucidated. Given a possible link between oral contraceptives (OCPs) and cervical cancer, estrogen and HPV may have synergistic roles in cervical tumorigenesis. The purpose of this study is to determine the role of the estrogen receptor in regulating the growth of cervical cancer cells. Study Design: Four cervical cancer cell lines, two HPV+ (SiHa and ME180) and two HPV- (HT-3 and C33A) were cultured under standard conditions and in phenol red free media supplemented with 10% charcoal/dextran stripped fetal bovine serum and antibiotics. These cell lines were subsequently treated in a dose-dependent manner (0- and 0.1- to 103-nM) with estradiol-17\#946; (E2), the estrogen receptor (ER)-\#945; agonist, 4,4',4''-(propyl-[ (1)H]-pyrazole-1,3,5-triyl) trisphenol (PPT), and the ER\#946; agonist, 2,3-bis (4-hydroxyphenyl) propionitrile (DPN) to determine the ability of these peptides to regulate cellular growth.. Cell lines were also treated with epidermal growth factor (EGF) as a positive control. A tetrazolium-based assay was used to determine the effect these compounds had on cell proliferation. Differences in cell proliferation were determined by an analysis of variance (ANOVA) followed by a post hoc comparison using Fisher LSD (significance at p<0.05). Results: EGF had a proliferative effect on all cell lines at both 24 hr and 72 hr. While the effect of EGF is consistent at both 24 hr and 72 hr for both HPV+ and HPV- cell-lines, the effect of E2 was similar at 24 hr but not at 72 hr. E2 increased (p<0.10) cellular proliferation up to 25% when compared to vehicle (VEH)-treated cells after 24 hr in all 4 cell lines. At 72 hr, E2 robustly increased cellular proliferation in both HPV+ cell lines, (p<0.05). HPV+ cell lines, ME180 and SiHa, demonstrated a 249% (95% CI = 188%-310%) and 226% (95% CI= 198%-254%) increase in proliferation over VEH, respectively but HPV- cell lines, HT-3 and C33A, only demonstrated a 102% (95%CI = 96%-108%) and 96% (95% CI = 69%-123%) increase in proliferation over VEH. Interestingly, PPT, a selective ER\#945; agonist, had proliferative effects in both HPV+ and HPV- cells that paralleled the effect of E2 at 72 hr. There was no consistent proliferative effect observed for DPN, a selective ER\#946; agonist, (p<0.10) on both HPV+ and HPV- cells. Conclusion: This is the first study to evaluate the effect of ER\#945; and ER\#946; on the proliferation of cervical cancer cells. The results from the present study suggest that E2 may have a selective proliferative effect in HPV+ cells compared to HPV- cells and that this effect may be mediated via ER\#945;. This apparent robust proliferative effect of E2 on HPV positive cell lines through ER\#945; could explain the epidemiologic link between OCPs and cervical cancer.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2381.