Skp2 and Jab1 Expression Are Associated with Inverse Expression of p27KIP1 and Poor Prognosis in Oral Squamous Cell Carcinomas
Skp2 and Jab1 Expression Are Associated with Inverse Expression of p27KIP1 and Poor Prognosis in Oral Squamous Cell Carcinomas
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DOI：
10.1159/000074649
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发表时间：
2003-12
期刊：
影响因子：
3.5
通讯作者：
S. Shintani;Chunnun Li;M. Mihara;S. Hino;K. Nakashiro;H. Hamakawa
中科院分区：
文献类型：
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作者：
S. Shintani;Chunnun Li;M. Mihara;S. Hino;K. Nakashiro;H. Hamakawa
先前的研究表明，低水平的p27 KIP1，G1细胞周期蛋白依赖性激酶（CDK）的抑制剂，与各种癌症的高侵袭性和预后不良相关。p27 KIP1水平降低至少部分是由Skp2（S期激酶相关蛋白2）和Jab1（Jun激活结构域结合蛋白1）加速降解引起的。本研究旨在探讨Skp2和Jab1的表达与p27 KIP1蛋白水平的相关性，以及它们在口腔鳞状细胞癌（OSCC）中的临床意义。Western blot分析p27KIP1与Skp2、Jab1表达的相关性。本文对75例口腔鳞癌进行了免疫组化分析。p27 KIP 1和Skp2、p27 KIP 1和Jab1的表达水平呈显著负相关（p < 0.0001）。因此，p27 KIP1水平的降低与Skp2和Jab1水平的强烈升高相关，而高水平的p27 KIP1与低水平的Skp2和Jab1相一致。p27 KIP 1表达降低、Skp 2和Jab1过表达与颈淋巴结转移和预后不良显著相关。Skp 2和Jab1的过度表达与p27 KIP 1表达的减少有关，并且可能在OSCC的进展中起作用。
Previous studies have shown that low levels of p27KIP1, an inhibitor of G1 cyclin-dependent kinases (CDK), are associated with high aggressiveness and poor prognosis in a variety of cancers. Decreased levels of p27KIP1 are caused, at least in part, by an acceleration of degradation with Skp2 (S-phase kinase-associated protein 2) and Jab1 (Jun activation domain-binding protein 1). This investigation was undertaken to examine whether the Skp2 and Jab1 expression is correlated with p27KIP1 protein levels, and how it is clinically relevant in oral squamous cell carcinoma (OSCC). The correlations between p27KIP1 and Skp2, and p27KIP1 and Jab1 expression were evaluated by Western blot analysis. Immunohistochemical analysis was done in 75 cases of OSCC. A strongly significant inverse correlation was found between levels of p27KIP1 and Skp2, and p27KIP1 and Jab1 (p < 0.0001). Thus, decreased levels of p27KIP1 were associated with strongly increased levels of Skp2 and Jab1, whereas high levels of p27KIP1 coincided with low levels of Skp2 and Jab1. Reductions of p27KIP1 expression and overexpression of Skp2 and Jab1 were significantly associated with cervical lymph node metastasis and poor prognosis. Overexpression of Skp2 and Jab1 is associated with the reduction of p27KIP1 expression, and may have a role in the progression of OSCC.