Effects of androgens on breast cancer cell migration and metastasis.

M.S. GIRETTI; L. GOGLIA; M.I. FLAMINI; A.M. SANCHEZ; P. MANNELLA; S. PISANESCHI; V. TOSI; A.R. GENAZZANI; T. SIMONCINI

March 5-8, Venezia, Italy

Congreso; 13th World Congress on Human Reproduction.; 2009

Androgens are used in postmenopausal hormonal regimens, but little is known about the effects of these sex hormones on the breast, particularly on breast cancer cell migration and metastasis. We studied the actions of testosterone (T), of the non-aromatizable dihydrotestosterone (DHT) and of dehydroepiandrosterone (DHEA) on actin cytoskeleton and cell movement through the activation of actin-binding protein, moesin. By using androgen receptor (AR) positive and estrogen receptor (ER) positive T47-D breast cancer cells, we showed that actin remodeling is induced by all the androgens studied but only at supraphysiological concentrations. Moreover, the effects of T and DHEA are counteracted not only by the anti-androgen flutamide but also by the pure ER antagonist ICI 182,780 and by the aromatase inhibitor DL-aminoglutethimide supporting the hypothesis of a central role in moesin phosphorylation by androgen conversion to estrogens and suggesting a possible implication of ER in moesin recruitment. Moreover, DHEA effect is blocked by flutamide and aminoglutethimide to a minor extent respect to T supporting the hypothesis that this steroid might act binding directly to ER. Conversely, DHT being not convertible in estrogen induces moesin activation only through AR. On the other hand, the androgenic signaling through AR does not induce cell movement promotion at physiological androgens concentrations. In conclusion, our results suggest that breast cancer cell motility induction by androgens might be mediated both directly through AR recruitment and indirectly after conversion to estrogens and linkage to ER. Research addressing the effects of androgens is warranted to ameliorate the knowledge on complex molecular mechanism of androgenic action and increase the safety of hormonal therapies.