Alterations in the expression of the cell cycle regulatory protein cyclin kinase subunit 1 in colorectal carcinoma -: Relation to p27Kip1 and its ubiquitin ligase subunit, S phase kinase protein 2
Alterations in the expression of the cell cycle regulatory protein cyclin kinase subunit 1 in colorectal carcinoma -: Relation to p27Kip1 and its ubiquitin ligase subunit, S phase kinase protein 2
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DOI：
10.1002/cncr.20172
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发表时间：
2004-04-15
期刊：
影响因子：
6.2
通讯作者：
Hershko, DD
中科院分区：
文献类型：
--
作者：
Shapira, M;Ben-Izhak, O;Hershko, DD
背景。 p27(Kip1) 水平低与多种恶性肿瘤（包括结直肠癌）的高侵袭性和不良预后相关。作者表明，S 期激酶蛋白 2 (Skp2)（一种以 p27 (Kip1) 为目标进行降解的特异性泛素连接酶亚基）在结直肠癌患者中过度表达，并且与 p27 (Kip1) 水平呈负相关。最近发现了细胞周期蛋白激酶亚基 1 (Cks1) 在 Skp2 依赖性 p27 降解中的重要作用，但其在人类恶性肿瘤中的作用尚不清楚。通过在十二烷基硫酸钠-聚丙烯酰胺凝胶上电泳分离来自 30 名患者的速冻结直肠肿瘤样本，转移到硝酸纤维素上，并用针对 Cks1、Skp2 和 p27 (Kip1) 的高度特异性单克隆抗体进行探测。还使用来自同一患者的福尔马林固定、石蜡包埋的组织切片，通过免疫组织化学检查了 Cks1 的表达。 结果。研究发现 Cks1 水平和 Skp2 表达与肿瘤分化丧失之间存在很强的相关性。 Cks1 和 p27 (Kip1) 水平与总生存期之间也观察到显着的负相关。结论。目前的研究结果表明，在侵袭性结直肠癌患者中，Cks1 表达增加可能在 p27 水平降低中具有重要的致病作用。 (C) 2004 年美国癌症协会。
BACKGROUND. Low levels of p27(Kip1) are associated with high aggressiveness and poor prognosis in various malignancies, including colorectal carcinoma. The authors showed that S phase kinase protein 2 (Skp2), the specific ubiquitin ligase subunit that targets p27(Kip1) for degradation, was overexpressed and was inversely related to p27(Kip1) levels in patients with colorectal carcinoma. The essential role of cyclin kinase subunit 1 (Cks1) in Skp2-dependent p27 degradation was recently discovered, but its role in human malignancies is unknown.METHODS. Quick-frozen colorectal tumor samples from 30 patients were separated by electrophoresis on sodium dodecyl sulfate-polyacrylamide gels, transferred to nitrocellulose, and probed with highly specific monoclonal antibodies directed against Cks1, Skp2, and p27(Kip1). The expression of Cks1 was also examined by immunohistochemistry using formalin-fixed, paraffin-embedded tissue sections from the same patients.RESULTS. A strong correlation was found between Cks1 levels and Skp2 expression and loss of tumor differentiation. A significant inverse relation was also observed between levels of Cks1 and p27(Kip1) and overall survival.CONCLUSIONS. The results of the current study suggest that increased expression of Cks1 may have an important causative role in decreasing levels of p27 in patients with aggressive colorectal carcinoma. (C) 2004 American Cancer Society.