RESUMO
Metastatic breast cancer is one of the most common metastatic tumors. Although studies have validated the role of ß-inducible gene-h3 (ßig-h3) in human biology and disease, the detailed mechanisms mediated by ßig-h3 in breast carcinoma metastasis remain unclear. Thus, the present study investigated the role and potential mechanism of ßig-h3 during breast carcinoma cell metastasis. The results indicated that the upregulation of ßig-h3 significantly promotes the growth and inhibits the cisplatin-induced apoptosis of breast carcinoma cells. It was also demonstrated that ßig-h3 promoted the migration and invasion of human breast carcinoma cells in vitro and in vivo. Furthermore, the results demonstrated that ßig-h3 upregulated the overall expression and phosphorylation of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) in human breast carcinoma cells. By contrast, ßig-h3 knockdown reversed the ßig-h3-mediated characteristics of breast carcinoma cells. Thus, the current study demonstrated that the PI3K/Akt signaling pathway serves a role in ßig-h3-induced human breast cancer cell metastasis and that ßig-h3 transfection enhances the metastatic potential of human breast carcinoma cells via the PI3K/Akt signaling pathway. These observations contribute to the understanding of the potential mechanism of human breast carcinoma cell growth and metastasis and suggest that ßig-h3 may be a promising therapeutic target for the treatment of human breast carcinoma.
RESUMO
PURPOSE: Many studies have investigated the association between CASP8-652 6N del polymorphism and the risk of breast cancer, but the result is still unclear owing to the obvious inconsistence among those studies. This study aims to quantify the strength of association between CASP8-652 6N del polymorphism and risk of breast cancer. METHODS: We searched the electronic MEDLINE database for studies relating to the association between CASP8-652 6N del polymorphism and risk of breast cancer. We estimated summary odds ratios (ORs) with their 95% confidence intervals (95% CIs) to assess the association. Ten case-control studies with 13,220 cases and 13,750 controls were included into this meta-analysis. RESULTS: Meta-analysis of a total of ten studies showed that reduced breast cancer risk was associated with CASP8 -652 6N del polymorphism (homozygous: OR=0.85, 95% CI 0.93-0.98). After adjustment for heterogeneity, meta-analysis showed that reduced breast cancer risk was also associated with CASP8-652 6N del polymorphism (homozygous: OR=0.78, 95% CI 0.63-0.95, dominant: OR=0.93, 95% CI 0.88-0.99). For Caucasians, CASP8-652 6N del was associated with reduced breast cancer risk at a borderline level (homozygous: OR=0.94, 95% CI 0.86-1.02, heterozygous: OR=0.96, 95% CI 0.90-1.03, recessive: OR=0.96, 95% CI 0.90-1.03, dominant: OR=0.94, 95% CI 0.88-1.01). No evidence of publication bias was observed. CONCLUSION: Meta-analyses of the available data suggest that CASP8 -652 6N del polymorphism is associated with reduced breast cancer risk.