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

xlomafota13 shared this article with you from Inoreader SERMs suppresses the growth of ERalpha positive cervical cancer xenografts through predominant inhibition of extra-nuclear ERalpha expression Via American Journal of Cancer Research Am J Cancer Res. 2021 Jun 15;11(6):3335-3353. eCollection 2021. ABSTRACT 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 ERα+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 ERα+ve MS751 CC xenografts, while SERMs and EGCG significantly decreased tumor formation. SERMs were found to inhibit ERα expression, localized within cytoplasmic and mem brane compartments. Conversely, ERα was not inducible and EE administration suppressed the growth of ERα-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 ERα has promoted CC tumorigenesis. This in turn was modulated by SERMs, predominantly through inhibition of extra-nuclear ERα expression. Though, induction of hyper-estrogenic status in the ectocervix, might underrate the utility of SERMs in ERα+ve CC. PMID:34249466 | PMC:PMC8263693 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.