The expression of the ubiquitin ligase subunit Cks1 in human breast cancer.
The expression of the ubiquitin ligase subunit Cks1 in human breast cancer.
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DOI：
10.1186/bcr1278
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Hershko DD
中科院分区：
文献类型：
--
作者：
Slotky M;Shapira M;Ben-Izhak O;Linn S;Futerman B;Tsalic M;Hershko DD
细胞周期抑制蛋白p27 Kip 1的缺失与乳腺癌预后不良相关这种蛋白水平的降低是蛋白酶体依赖性降解增加的结果，由其特异性泛素连接酶亚基S期激酶蛋白2（Skp 2）和细胞周期蛋白依赖性激酶亚基1（Cks 1）介导和限速。最近发现Skp 2在乳腺癌中过表达，但Cks 1在这些癌症中的作用尚不清楚。本研究旨在探讨Cks 1表达在乳腺癌中的作用及其与p27 Kip 1和Skp 2表达和肿瘤侵袭性的关系。Cks 1，Skp 2和p27 Kip 1的表达检测化学福尔马林固定，石蜡包埋的组织切片从50例乳腺癌患者和乳腺癌细胞系的免疫印迹分析。采用考克斯回归和Kaplan-Meier法分析Cks 1水平与患者临床和组织学参数的关系。Cks 1与Skp 2的表达呈强相关（r = 0.477; P = 0.001），与p27 Kip 1的表达呈负相关（r = -0.726; P < 0.0001）。Cks 1的过表达与肿瘤分化丧失、年轻、雌激素受体和孕激素受体表达缺乏以及无病生存期（P = 0.0007）和总体生存期（P = 0.041）下降相关。此外，Cks 1和Skp 2的表达增加了雌激素依赖性细胞系中的雌二醇，但下调他莫昔芬。这些结果表明，Cks 1参与了p27 Kip 1的下调，并可能在乳腺癌侵袭性肿瘤行为的发展中发挥重要作用。
Loss of the cell-cycle inhibitory protein p27Kip1 is associated with a poor prognosis in breast cancer. The decrease in the levels of this protein is the result of increased proteasome-dependent degradation, mediated and rate-limited by its specific ubiquitin ligase subunits S-phase kinase protein 2 (Skp2) and cyclin-dependent kinase subunit 1 (Cks1). Skp2 was recently found to be overexpressed in breast cancers, but the role of Cks1 in these cancers is unknown. The present study was undertaken to examine the role of Cks1 expression in breast cancer and its relation to p27Kip1 and Skp2 expression and to tumor aggressiveness. The expressions of Cks1, Skp2, and p27Kip1 were examined immunohistochemically on formalin-fixed, paraffin-wax-embedded tissue sections from 50 patients with breast cancer and by immunoblot analysis on breast cancer cell lines. The relation between Cks1 levels and patients' clinical and histological parameters were examined by Cox regression and the Kaplan–Meier method. The expression of Cks1 was strongly associated with Skp2 expression (r = 0.477; P = 0.001) and inversely with p27Kip1 (r = -0.726; P < 0.0001). Overexpression of Cks1 was associated with loss of tumor differentiation, young age, lack of expression of estrogen receptors and of progesterone receptors, and decreased disease-free (P = 0.0007) and overall (P = 0.041) survival. In addition, Cks1 and Skp2 expression were increased by estradiol in estrogen-dependent cell lines but were down-regulated by tamoxifen. These results suggest that Cks1 is involved in p27Kip1 down-regulation and may have an important role in the development of aggressive tumor behavior in breast cancer.
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影响因子：
6.2
作者：
Shapira, M;Ben-Izhak, O;Hershko, DD
通讯作者：
Hershko, DD
影响因子：
9.2
作者：
Tsvetkov, LM;Yeh, KH;Zhang, H
通讯作者：
Zhang, H
影响因子：
21.3
作者：
Carrano, AC;Eytan, E;Pagano, M
通讯作者：
Pagano, M
影响因子：
6.2
作者：
Shapira, M;Ben-Izhak, O;Hershko, DD
通讯作者：
Hershko, DD
影响因子：
21.3
作者：
Ganoth, D;Bornstein, G;Hershko, A
通讯作者：
Hershko, A