Jab1的表达与p27（kip1）的反向表达以及上皮性卵巢肿瘤的不良预后相关。

Jab1 expression is associated with inverse expression of p27(kip1) and poor prognosis in epithelial ovarian tumors.

作者信息

Sui L, Dong Y, Ohno M, Watanabe Y, Sugimoto K, Tai Y, Tokuda M

机构信息

Department of Perinato-Gynecology, Kagawa Medical University, 1750-1 Ikenobe, Miki-Cho, Kida-Gun, Kagawa 761-0793, Japan.

出版信息

Clin Cancer Res. 2001 Dec;7(12):4130-5.

DOI:

PMID:11751512

Abstract

PURPOSE

Jab1 (Jun activation domain-binding protein 1) has been described as a coactivtor of AP1 transcription factor, and is a subunit of a large protein complex (called the COP9 signalosome). Recent study (K. Tomoda et al., Nature (Lond.), 398: 160-165, 1999) found that Jab1 protein can cause breakdown of p27(kip1) protein in mammalian cells. To investigate whether Jab1 expression is correlated with p27(kip1) protein levels as well as how it might be clinically relevant, we evaluated the expression of Jab1 in a group of epithelial ovarian tumors.

EXPERIMENTAL DESIGN

Immunohistochemical analysis was performed in 80 cases of ovarian tumors (33 benign ovarian tumors and 47 ovarian carcinomas). Twenty-six of the 80 cases were evaluated by Western blot analysis.

RESULTS

Jab1 overexpression was detected in 68.1% (32 of 47) of malignant tumors and 33.3% (11 of 33) of benign tumors. The positive ratio of Jab1 was increased from benign to malignant ovarian tumors (P = 0.002). A negative correlation between Jab1 and p27(kip1) expression was found in both benign (P = 0.003) and malignant (P = 0.002) ovarian tumors. No significant correlation was observed between Jab1 overexpression and clinicopathological parameters. Kaplan-Meier survival analysis showed that Jab1 overexpression was significantly associated with poor prognosis of patients (P = 0.049).

CONCLUSIONS

Jab1 expression is inversely correlated with p27(kip1) expression levels, and Jab1, as a negative regulator of p27(kip1), may be associated with the progression and prognosis of epithelial ovarian tumors.

摘要

目的

Jab1（Jun激活域结合蛋白1）已被描述为AP1转录因子的共激活因子，并且是一种大型蛋白质复合物（称为COP9信号体）的一个亚基。最近的研究（K. Tomoda等人，《自然》（伦敦），398: 160 - 165，1999）发现Jab1蛋白可导致哺乳动物细胞中p27（kip1）蛋白的降解。为了研究Jab1表达是否与p27（kip1）蛋白水平相关以及它在临床上可能有何关联，我们评估了一组上皮性卵巢肿瘤中Jab1的表达情况。

实验设计

对80例卵巢肿瘤（33例良性卵巢肿瘤和47例卵巢癌）进行了免疫组织化学分析。80例中的26例通过蛋白质印迹分析进行评估。

结果

在68.1%（47例中的32例）的恶性肿瘤和33.3%（33例中的11例）的良性肿瘤中检测到Jab1过表达。Jab1的阳性率从良性卵巢肿瘤到恶性卵巢肿瘤呈上升趋势（P = 0.002）。在良性（P = 0.003）和恶性（P = 0.002）卵巢肿瘤中均发现Jab1与p27（kip1）表达呈负相关。未观察到Jab1过表达与临床病理参数之间存在显著相关性。Kaplan - Meier生存分析表明，Jab1过表达与患者的不良预后显著相关（P = 0.049）。