Significance of Jab1 expression in human esophageal squamous cell carcinoma.
OBJECTIVE
The aim of the present study was to examine the expression of Jun activation domain-binding protein 1(Jab1) and p27 and to elucidate its clinicopathologic significance in a larger series of squamous cell carcinoma (SCC) of the esophagus.


BACKGROUND
Reduced expression of p27 has been associated with poor prognosis in most human cancers, including esophageal SCCs. Jab1 is known as a coactivator of AP-1 transcription factor, which contributes to tumor progression by degrading the p27 protein.


METHODS
Immunohistochemical and Western blot analysis were performed in 90 cases of esophageal SCCs and ECA109 cells. Survival analyses were performed by using the Kaplan-Meier method.


RESULTS
Immunohistochemical analysis showed that Jab1 expression was negatively associated with p27 level and significantly associated with unfavorable clinicopathologic variables. Overexpression of Jab1 in ECA109 cells resulted in decreased p27 level and this decrease was sensitive to 26S proteasome inhibitors. Subcellular fractionation confirmed Jab1 could lead to nuclear export of p27. Survival analysis revealed that Jab1 overexpression was significantly associated with overall survival (P<0.001). When Jab1 and p27 are combined, patients with Jab1(+)/p27(-) revealed poorer overall survival (P<0.001), what's more, patients with the phenotype of Jab1(+)/lymph node(+) had poorer disease-free and overall survival than others (P<0.001).


CONCLUSIONS
These findings suggest that Jab1 is involved in the pathogenesis of esophageal SCC and that elevated levels of Jab1 expression may indicate a poor prognosis for patients with esophageal SCC.
Department of Cardiovascular Surgery, Shanghai JiaoTong University Affiliated First People's Hospital, Shanghai, P.R. China.
Feng
F
Wang
Yuchan
Y
Wang
Xiaowei
X
Yu
Dicheng
D
Yang
Zheng
Z
Wang
Chengbao
C
Lu
Zhongxiang
Z
Yuan
Mingdi
M
Xiao
Aiguo
A
Shen
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D000075686:COP9 Signalosome Complex; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor / Q000378:metabolism / Q000473:pathology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex