Effects of raloxifene and estrogen on breast cancer cell migration and invasion.

M. FLAMINI; A.M. SANCHEZ; S. GARIBALDI; C. BALDACCI; M.S. GIRETTI; X.D. FU; L. GOGLIA; A.R. GENAZZANI; T. SIMONCINI

May 19-23, Madrid, España

Congreso; 12th World Congress on the Menopause.; 2008

INTERNATIONAL MENOPAUSE SOCIETY

Estrogens and SERMs have differential effects on breast cancer cell division and cancer growth, but little is known on the effects on breast cancer cell migration, invasion and metastasis. We used ER-positive human breast cancer cells to study the effects of estrogens or SERMs on cell movement and we characterized the molecular events that mediate these actions. In T47D cells, estradiol (E2) induces a rapid remodeling of cortical actin associated with migration and invasion. These effects are mediated by the activation of the actin binding protein, moesin. Moesin activation by E2 relies on the recruitment of a cell membrane estrogen receptor- (ER ). Activated ER interacts with G 13 at the cell membrane, and activates the signaling to RhoA and Rho-associated Kinase 2, that phosphorylates moesin. Raloxifene (RAL) administration to T47D cells is also associated with a weak and transient activation of this pathway. When RAL is used in co-treatment with E2, a strong inhibition of the activation of moesin and of cytoskeletal remodelling are seen, suggesting that this SERM may antagonize breast cancer cell migration induced by E2. Estrogen directs the interaction with the extracellular environment and the movement of T47D cells through the regulation of the assembly of the actin cytoskeleton. RAL alter this signaling of estradiol, which may translate in reduced migration of breast cancer cells in the presence of estrogens. These findings increase our understanding of breast cancer cell biology and may have clinical relevance for the development of new therapeutic strategies for the prevention or control of breast cancer. Estrogens and SERMs have differential effects on breast cancer cell division and cancer growth, but little is known on the effects on breast cancer cell migration, invasion and metastasis. We used ER-positive human breast cancer cells to study the effects of estrogens or SERMs on cell movement and we characterized the molecular events that mediate these actions. In T47D cells, estradiol (E2) induces a rapid remodeling of cortical actin associated with migration and invasion. These effects are mediated by the activation of the actin binding protein, moesin. Moesin activation by E2 relies on the recruitment of a cell membrane estrogen receptor- (ER ). Activated ER interacts with G 13 at the cell membrane, and activates the signaling to RhoA and Rho-associated Kinase 2, that phosphorylates moesin. Raloxifene (RAL) administration to T47D cells is also associated with a weak and transient activation of this pathway. When RAL is used in co-treatment with E2, a strong inhibition of the activation of moesin and of cytoskeletal remodelling are seen, suggesting that this SERM may antagonize breast cancer cell migration induced by E2. Estrogen directs the interaction with the extracellular environment and the movement of T47D cells through the regulation of the assembly of the actin cytoskeleton. RAL alter this signaling of estradiol, which may translate in reduced migration of breast cancer cells in the presence of estrogens. These findings increase our understanding of breast cancer cell biology and may have clinical relevance for the development of new therapeutic strategies for the prevention or control of breast cancer.