The expression and prognosis of Emi1 and Skp2 in breast carcinoma: associated with PI3K/Akt pathway and cell proliferation
The expression and prognosis of Emi1 and Skp2 in breast carcinoma: associated with PI3K/Akt pathway and cell proliferation
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DOI：
10.1007/s12032-013-0735-0
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发表时间：
2013-12-01
期刊：
影响因子：
3.4
通讯作者：
Ni, Qichao
中科院分区：
文献类型：
--
作者：
Liu, Xiaobing;Wang, Hua;Ni, Qichao
S相激酶2(Skp2)是一种致癌蛋白，在乳腺癌中过表达。本研究旨在探讨早期有丝分裂抑制因子-1(Emi1)过表达对乳腺癌Skp2表达及相关信号转导途径的影响。对98例乳腺癌标本进行了免疫组织化学分析，并与临床病理特征进行了比较。此外，对乳腺癌标本和细胞系中的Emi1和Skp2进行Western印迹分析，以评估它们的蛋白水平和分子相互作用。研究发现，Emi1的表达与Skp2的表达呈正相关(P<0.005)，且Emi1的表达与组织学分级显著相关(P=0.05)，Skp2的表达也有相似的结果。Kaplan-Meier分析显示，在乳腺癌中，Emi1和Skp2低表达和高表达的生存曲线显示高度显著的分离(P<；0.01)。而在体外，乳腺癌细胞株从血清饥饿中释放后，Emi1、Skp2、磷酸化Akt(p-Akt)的表达上调，而p27(Kip1)的表达下调。磷脂酰肌醇3-激酶(PI3K)抑制剂LY294002可抑制细胞生长，降低Emi1的表达。这些结果提示EMI1的S抗凋亡和增殖能力似乎至少部分是由Skp2的调节触发的，EMI1和Skp2的联合表达可能是浸润性乳腺癌患者的预后指标，这也与p-Akt和激活的p27(Kip1)降解有关。Emi1可能成为针对PI3K治疗乳腺癌的一种潜在治疗策略。
S-phase kinase protein 2 (Skp2) is oncogenic and overexpressed in human breast cancer. The objective of this study was to examine the effect of early mitotic inhibitor-1 (Emi1) over-expression on Skp2 expression and related signaling pathway in breast cancer. Immunohistochemical analysis was performed in 98 human breast carcinoma samples and the data were correlated with clinicopathologic features. Furthermore, Western blot analysis was performed for Emi1 and Skp2 in breast carcinoma samples and cell lines to evaluate their protein levels and molecular interaction. We found that the expression of Emi1 was positively related with Skp2 expression (P < 0.01) and Emi1 expression correlated significantly with histologic grade (P = 0.005), meanwhile Skp2 expression obtained similar results. Kaplan-Meier analysis revealed that survival curves of low versus high expressers of Emi1 and Skp2 showed a highly significant separation in human breast cancer (P < 0.01). While in vitro, following release of breast cancer cell lines from serum starvation, the expression of Emi1, Skp2, phosphor-Akt (p-Akt) was up-regulated, whereas p27(Kip1) was down-regulated. Treatment of phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 could arrest cells growth and diminish Emi1 expression. These results suggested that Emi1's anti-apoptotic and proliferative abilities appear to be triggered at least in part by the modulation of Skp2, combined Emi1 and Skp2 expressions, may be prognostic for patients with invasive breast carcinomas, which also associated with p-Akt and enabled p27(kip1) degradation. Emi1 may serve as a potential therapeutic strategy aimed at PI3K for the management of breast cancer.