Expression of Jun activation domain-binding protein 1 and Ser10 phosphorylated p27 protein in human epithelial ovarian carcinoma.
OBJECTIVE
The aim of the present study was to examine whether Jab1 expression is correlated with p27 protein and its phosphorylation status as well as how it might be clinically relevant in epithelial ovarian carcinoma. Using ovarian carcinoma cell line HO-8910 to confirm and extend the findings.


METHODS
Immunohistochemical and Western blot analysis were done in 70 cases of epithelial ovarian cacinoma and HO-8910 cells.


RESULTS
Jab1 overexpression was detected in 84.3% (59 of 70) of malignant tumors and 31.6% (6 of 19) of benign tumors. A positive correlation between Jab1 and cytoplasmic p27 as well as Ser10 phosphorylated p27 was found in malignant ovarian tumors. In addition, patients displaying overexpression of Jab1, cytoplasmic p27 and Ser10 phosphorylated p27 were significantly associated with unfavorable clinicopathologic variables. Transfection with Jab1 in HO-8910 cells resulted in decreased p27 expression and this reduction was sensitive to 26S proteasome inhibitors. Overexpression of Jab1 caused p27 nuclear export and dissociate from Cdk2/Cyclin complex. What is more, increased expression of a phosphorylated histone H1 in the immune-complex obtained from Jab1 transfected HO-8910 cells was also observed.


CONCLUSIONS
Jab1, as a negative regulator of p27, may be associated with the progression and prognosis of epithelial ovarian tumors.
Wang
You
Y
Department of Pathology, Affiliated Cancer Hospital of Nantong University, Medical College of Nantong University, Nantong, People's Republic of China.
Wang
Yuchan
Y
Cheng
Chun
C
Ji
Yuhong
Y
Zhao
Yueming
Y
Zou
Lin
L
Shen
Aiguo
A
D000328:Adult; D000368:Aged; D000075686:COP9 Signalosome Complex; D002278:Carcinoma in Situ / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011379:Prognosis; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D047908:Intracellular Signaling Peptides and Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D012694:Serine; D017346:Protein Serine-Threonine Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex