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


METHODS
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.
Sui
L
L
Department of Perinato-Gynecology, Kagawa Medical University, 1750-1 Ikenobe, Miki-Cho, Kida-Gun, Kagawa 761-0793, Japan.
Dong
Y
Y
Ohno
M
M
Watanabe
Y
Y
Sugimoto
K
K
Tai
Y
Y
Tokuda
M
M
D000075686:COP9 Signalosome Complex; D002277:Carcinoma / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D018797:Cell Cycle Proteins / Q000032:analysis / Q000235:genetics*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D010447:Peptide Hydrolases; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000235:genetics*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex