Rapid signals from estrogens and SERMs involved in endometrial cell migration and invasion.

M.I. FLAMINI; A.M. SANCHEZ; A.R. GENAZZANI; T. SIMONCINI

March 4-7, FIRENZE, ITALY.

Congreso; 14th World Congress of Gynecological Endocrinology, II Congresso ISGE Italia; 2010

INTERNATIONAL SOCIETY OF GYNECOLOGICAL ENDOCRINOLOGY (ISGE)

Cancer and normal cells possess a broad spectrum of migration and invasion mechanisms that are critical for endometrial cells, not only for the establishment of pathological states such as metastasis but also during the physiological conditions that occurs during the menstrual cycle and embryo implantation. Cells movement involves dynamic filamentous actin cytoskeletal remodeling and disassembly of focal adhesion sites. Rapid activation of intracellular signalling cascades ER/Gá13/RhoA/ROCK/moesin by estrogens is involved in the migration of much kind of cells. Although estrogen is recognized to induce cell migration in some model systems, very little information is available regarding the potential influence of selective estrogen receptor modulators, tamoxifen (TAM) or raloxifene (RAL), on these processes. For these reason, we have investigated the effects of E2, TAM or RAL in endometrial cancer and normal human endometrial stromal cells. Ours results indicate that rapid treatment (15min) with both E2 and TAM significantly increased phosphorylation of moesin and induce actin cytoskeleton arrangement. Conversely, raloxifene did not interfere with the basal actin organization but inhibits the E2-induced it. Learning more about the cellular and molecular basis of these different migration/invasion programmes will help us to understand how cancer cells disseminate and lead to new treatment strategies.