Regulation of ERM protein-dependent cytoskeletal remodelling, cell migration and invasion by estetrol (E4) in human breast cancer cell.

M.S. GIRETTI; X.D. FU; P. MANNELLA; C. BALDACCI; S. GARIBALDI; A. CARUSO; M. FLAMINI; A.M. SANCHEZ; E. LENZI; S. BEGLIUOMINI; A.R. GENAZZANI; T. SIMONCINI

8-11 March, Rome, Italy

Congreso; The 2nd World Congress on Gender-Specific Medicine and Ageing. The Endocrine Impact.; 2007

Estetrol (E4) is an estrogen metabolite that is produced by the human fetus during the uterine life and circulates in the unborn child and the mother. E4 derives from DHEA sulfate and estradiol sulfate after a liver modification. Even if E4 has been supposed to have a protective action against breast cancer, no conclusive data have been published. Particularly, few is known about the molecular mechanisms of action by which estetrol could exert this action. In a previous paper, we have already described in T47-D breast cancer cells how 17beta-estradiol induces rapid and dynamic actin cytoskeleton remodelling which leads cell movement through the activation of the actin-regulatory protein, moesin. In this study, we compare the effects of 17beta-estradiol (E2) and E4 on T47-D breast cancer cell migration and invasion via the regulation of moesin. Whereas E2 induces rapid actin remodelling initiated by moesin activation, E4 alone shows a weak estrogenic activity. On the contrary, estetrol plus estradiol treatment counteracts promoting effect of E2 on T47-D cell migration and invasion which depends on moesin recruitment. In conclusion, E4 reduces estradiol dependent actin remodeling and movement and invasion of breast cancer cells via moesin activation. These findings may represent a new therapeutically tool to interfere with steroid-dependent breast cancer cell metastasis.