<i>In vivo</i> and <i>in vitro</i> estrogenic and progestagenic actions of Tibolone

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dc.contributor.authorSadarangani, A
dc.contributor.authorSalgado, AN
dc.contributor.authorKato, S
dc.contributor.authorPinto, M
dc.contributor.authorCarvajal, A
dc.contributor.authorMonso, C
dc.contributor.authorOwen, GI
dc.contributor.authorVigil, P
dc.date.accessioned2025-01-21T01:07:18Z
dc.date.available2025-01-21T01:07:18Z
dc.date.issued2005
dc.description.abstractEstrogen and progestin combination in hormone replacement therapy (HRT) increases the incidence of breast cancer, but decreases the endometrial cancer risk of unopposed estrogen. Therefore, a SERM such as Tibolone, that delivers the beneficial, but not the adverse side effects, of steroid hormones would be clinically advantageous. However, data from the Million Women Study suggests that Tibolone increases the risk of both breast and endometrial cancer. Herein, we assessed the estrogenic and progestagenic actions of Tibolone using transvaginal sonography studies and an in vitro model of breast (ZR-75, MCF7) and endometrial cancer (Ishikawa). The known cancer associated proteins (ER, EGFR, STAT5, tissue factor and Bcl-xL) were selected for study. Transvaginal sonography demonstrated that postmenopausal women treated with Tibolone displayed a thinner endometrium than in the late proliferative phase, but had a phenotype characteristic of the secretory phase, thus demonstrating the estrogenic and progestagenic actions of this SERM. In vitro, Tibolone acted as an estrogen in downregulating ER and upregulating Bcl-xL, yet as progesterone, increasing STAT5 and tissue factor in breast cancer cells. The increase in tissue factor by Tibolone correlated with its coagulative potential. Interestingly, EGFR was Lip-regulated by progesterone in the breast and by estrogen in endometrial cells, while Tibolone increased protein levels in both cell types. In conclusion, this study further demonstrates the estrogenic and progestagenic nature of Tibolone. The pattern of regulation of known oncogenes in cells of breast and endometrial origin dictates caution and vigilance in the prescription of Tibolone and subsequent patient monitoring.
dc.description.funderWellcome Trust
dc.fuente.origenWOS
dc.identifier.eissn0717-6287
dc.identifier.issn0716-9760
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/96306
dc.identifier.wosidWOS:000232626700014
dc.issue.numero2-3
dc.language.isoen
dc.pagina.final258
dc.pagina.inicio245
dc.revistaBiological research
dc.rightsacceso restringido
dc.subjectbreast/endometrium cancer
dc.subjectestrogenic
dc.subjectHRT
dc.subjectprogestagenic & tibolone
dc.subject.ods03 Good Health and Well-being
dc.subject.ods05 Gender Equality
dc.subject.odspa03 Salud y bienestar
dc.subject.odspa05 Igualdad de género
dc.title<i>In vivo</i> and <i>in vitro</i> estrogenic and progestagenic actions of Tibolone
dc.typeartículo
dc.volumen38
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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