Role of calpain-fibronectin signaling inestrogen-induced migration in breast cancer cells / 中国药理学通报

ABSTRACT

Aim To study the effect of estrogen on the migration of breast cancer cells and the possible underlying mechanisms.Methods Human breast cancer cell lines MCF-7(estrogen receptor, ER+) and MDA-MB-468(ER-) were employed as a model system.Cells were treated with E2 and pretreated with CANP inhibitor(calpeptin)where needed.Wound-healing assay was applied to evaluate cell migration, Western blot assay was performed to observe protein level, and fibronectin expression was silenced by specific siRNA transfection.Results ① Treatmentof MCF-7 and MDA-MB-468 cellswith E2(50 nmol·L-1) increased cell migration by(51.55±5.50) ％(P<0.01)and (40.78±4.78)％(P<0.05), respectively;② E2 significantly up-regulated the expression of FN protein in MCF-7 and MDA-MB-468 breast cancer cells, which was 2.11 times(P<0.05)and 1.86 times(P<0.01), respectively;③ Pretreatment with calpeptin(10 μmol·L-1) decreased E2-induced cell migration by (49.55±6.44)％(P<0.05) in MCF-7 and(36.85±4.40)％ (P<0.01)in MDA-MB-468 cells;④ Calpeptin pretreatment inhibited E2-induced fibronectin up-regulation by(80.12±4.55)％ and(78.84±5.70) ％(P<0.01), respectively;⑤ Knockdown of FN with siRNA suppressed cell E2-induced migration by(40.65±5.80)％(P<0.01)in MCF-7 and(40.88±6.02)％(P<0.05)in MDA-MB-468 cells.Conclusion E2 stimulates the migration of breast cancer cells with or without ER expression and a calpain-FN signaling pathway may be involved in the E2 action.