Comparative actions of progesterone, medroxyprogesterone acetate and drospirenone on breast cancer cell migration and invasion.

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

Turin, Italy

Congreso; The Breast 2007. First International Congress on Breast Development, Functions and Diseases.; 2007

Hormone replacement therapy increases the risk of breast cancer. However, little is known on the effects of progestins on breast cancer cell movement and on the possible differences between the various available compounds. To this extent, we explored the effects of natural progesterone (P), medroxyprogesterone acetate (MPA) or drospirenone (DRSP), alone or in combination with 17beta-estradiol (E2) on cell migration and invasion and the signaling steps recruited by these compounds in T47D breast cancer cells. P, MPA and DRSP all increase the migration of breast cancer cells, with MPA being the most active and DRSP being markedly less active. In the presence of any of the three progestins, the addition of E2 slightly increases the migration of breast cancer cells over that achieved by progestin alone. The same happens when the ability of T47D cells to invade three-dimensional matrices is tested. These actions and the relative differences are related to the differential ability to recruit the actin-binding protein moesin by progesterone receptors. This leads to distinct effects on actin cytoskeleton remodeling and on the formation of cell membrane structures that mediate cell movement. In conclusion, we find that while progestins tested all enhance the tendency of breast cancer cells to migrate and invade, significant differences are present between the available molecules, that are related to differential effects on intracellular intermediates that regulate the cytoskeleton. These results support the concept that each progestin acts differently on the breast and may thus have relevant clinical implications.