SERMs suppresses the growth of ERα positive cervical cancer xenografts through predominant inhibition of extra-nuclear ERα expression

The role of estrogens and estrogen receptors (ER) in cervical cancer (CC) is not well established. However, epidemiological studies and abundant evidence from genetically engineered mouse models support such hypothesis. In this study, we have addressed estrogen responsiveness in a human CC cell line xenograft mouse model. We assessed the sensitivity of Ethynyl Estradiol (EE), SERMs (fulvestrant, MPP) and a non-SERM (EGCG) to competitively modulate the growth of ER alpha+(ve) MS751 CC xenografts. We also checked the agonistic-antagonistic propensity of the above treatments to alter the histology of ovariectomised mouse uterine cervix. Chronic EE treatment encouraged the growth of ER alpha+(ve) MS751 CC xenografts, while SERMs and EGCG significantly decreased tumor formation. SERMs were found to inhibit ER alpha expression, localized within cytoplasmic and membrane compartments. Conversely, ER alpha was not inducible and EE administration suppressed the growth of ER alpha-(ve) HeLa CC xenografts. SERMs competitively induced atrophic features to uterine cervix, with MPP giving rise to mucinous metaplasia in the ectocervix. We have demonstrated that, estrogen sensitivity mediated through ER alpha has promoted CC tumorigenesis. This in turn was modulated by SERMs, predominantly through inhibition of extra-nuclear ER alpha expression. Though, induction of hyperestrogenic status in the ectocervix, might underrate the utility of SERMs in ER alpha+(ve) CC.

Automated summary

The role of estrogens and estrogen receptors in cervical cancer is not well understood, but research suggests estrogen sensitivity and SERMs may impact tumor formation. SERMs and EGCG were found to decrease tumor growth, while chronic EE treatment promoted tumor growth in a mouse model.