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In vitro studies of tibolone in breast cells
Anne Gompel1, Marc Chaouat, Denis Jacob
1Unite Fonctionnelle de Gynécologie-endocrinienne, Hôpital Hôtel-Dieu AP-HP, Paris, France. anne.gompel@htd.ap-hop-paris.fr
Objective:
To investigate the effects of tibolone and its main metabolites on breast homeostasis.
Design:
In vitro studies in primary cultures of normal breast cells and in breast cancer cell lines.
Setting:
Hospital-based academic research center.
Patient(S):
Human breast cells were obtained from women undergoing surgery for hypermastia. Breast cancer cell lines (MCF-7, T47-D, and ZR75-1) were routinely obtained from subcultures.
Intervention(S):
Cells were incubated with tibolone, its various metabolites, the pure pregnane Org 2058, and the androgen dihydrotestosterone.
Main Outcome Measure(S):
Proliferation was determined by using a morphometric growth index, apoptosis by using morphologic analysis and flow cytometry, and antiapoptotic proteins bcl-2 and bclx(L) by using Western blot assay. Activity of 17beta-hydroxysteroid dehydrogenase was measured as an epithelial differentiation marker.
Result(S):
Tibolone and its delta(4) isomer were antiproliferative in normal breast cells. Tibolone and its delta(4) isomer increased apoptosis in breast cells. These proapoptotic effects were at least partially mediated through decreased expression of the antiapoptotic proteins bcl-2 and bclx(L). An increase in HSD activity was observed after tibolone administration.
Conclusion(S):
Tibolone is antiproliferative and proapoptotic and induces differentiation in normal breast cells. It is also proapoptotic in breast cancer cell lines.