The expression and prognosis of Emi1 and Skp2 in breast carcinoma: associated with PI3K/Akt pathway and cell proliferation
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- 作者：Xiaobing Liu (1)
Hua Wang (1)
Jing Ma (1)
Junfei Xu (1)
Chenyi Sheng (1)
Shuyun Yang (2)
Lingling Sun (1)
Qichao Ni (1) - 关键词：Emi1 ; Skp2 ; Breast cancer ; Prognosis ; PI3K/Akt
- 刊名：Medical Oncology
- 出版年：2013
- 出版时间：December 2013
- 年：2013
- 卷：30
- 期：4
- 全文大小：607 KB
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Hua Wang (1)
Jing Ma (1)
Junfei Xu (1)
Chenyi Sheng (1)
Shuyun Yang (2)
Lingling Sun (1)
Qichao Ni (1)
1. Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, People’s Republic of China
2. Department of Pathology, Affiliated Cancer Hospital of Nantong University, Medical College of Nantong University, Nantong, 226001, Jiangsu Province, People’s Republic of China - ISSN：1559-131X
文摘
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 p27Kip1 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 p27kip1 degradation. Emi1 may serve as a potential therapeutic strategy aimed at PI3K for the management of breast cancer.