关键词: 雌激素, 钙蛋白酶, 侵袭, p21, 周期蛋白E2

Abstract: Objective To investigate the effect of 17β-estradiol(E2) on the gene expression and coincident enhanced invasion, and the role of ERK-calpain signaling in the E2 action, withthe purpose ofstudyingthe molecular mechanism for the E2 effect. Methods MCF-7 breast cancer cells were used as a model system，RT-PCR was employed to evaluate levels of mRNA of target genes. Transwell invasion assay was applied to access cell invasive ability. Western blot was used to analyze the proteolysis of target proteins, and siRNA was used to knockdown calpain2 gene expression and reduce the activity of calpain. Results Treatment of MCF-7 cells with E2induced significant up-regulation of both p21 and CCNE2 (P<0.01), as well as enhanced invasion. Calpain or MEK specific inhibitors, calpeptin (10μM) and PD98059(10μM), showed tremendous suppression of E2-stimulated expression of p21 /CCNE2 mRNA (P<0.01）. Knockdown of calpain2 blocked E2-stimulated calpain activation and cell invasion (P<0.01). ConclusionsE2 induces up-regulation of p21/CNNE2 mRNA and enhances invasion and this effect is mediated via calpain, indicating calpaincould be a potential target for the prevention of metastatic breast cancer.

Key words: Estrogen, Calpain, Invasion, p21, Cyclin E2