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Jab1 Expression Is Associated with Inverse Expression of p27^kip1 and Poor Prognosis in Epithelial Ovarian Tumors¹

Departments of Perinato-Gynecology [L. S., M. O.] and Physiology [Y. D., Y. W., K. S., Y. T., M. T.], Kagawa Medical University, Kagawa 761-0793, Japan

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.

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