Expression of nucleostemin, epidermal growth factor and epidermal growth factor receptor in human esophageal squamous cell carcinoma tissues.
OBJECTIVE
To determine the expression of nucleostemin (NS), epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) mRNA in human esophageal squamous cell carcinoma (ESCC) tissues and their association in a human ESCC cell line.


METHODS
The expression of NS, EGF and EGFR mRNA was determined in paired normal esophageal and ESCC tissues of 62 patients using in situ hybridization. The association between NS and EGF or EGFR was examined using immunoblotting and real time polymerase chain reaction in a human ESCC cell line transfected with NS siRNA or treated with a selective EGFR inhibitor.


RESULTS
In normal esophageal and ESCC tissues, the positive detection rates were 21.0% (13/62) and 69.4% (43/62) for NS mRNA staining, 40.3% (25/62) and 77.4% (48/62) for EGF mRNA staining, and 30.6% (19/62) and 75.8% (41/62) for EGFR mRNA staining, respectively. These results indicated that NS, EGF and EGFR mRNA expression was upregulated mostly in ESCC tissues. Moreover, the expression of NS, EGF and EGFR mRNA was positively correlated with tumor grade, invasion and lymphatic metastasis of ESCC cells. NS mRNA was co-expressed with EGF and EGFR mRNA in ESCC tissues. The in vitro studies using a human ESCC cell line showed that knockdown of NS with NS siRNA significantly reduced EGF and EGFR expression. However, inhibition of the EGFR kinase activity with a specific EGFR kinase inhibitor had minimal effect on NS expression.


CONCLUSIONS
The upregulation of NS, EGF and EGFR mRNA frequently occurs in ESCC tissues and is associated with malignancy of human esophageal squamous tumors. NS is required for EGF and EGFR expression.
Zhang
Gongyuan
G
Department of Histology and Embryology, College of Basic Medical Sciences, Zhengzhou University, 100 Kexue Boulevard, 450001, Zhengzhou, People's Republic of China.
Zhang
Qiao
Q
Zhang
Qinxian
Q
Yin
Lei
L
Li
Shenglei
S
Cheng
Kuisheng
K
Zhang
Yunhan
Y
Xu
Honghui
H
Wu
Weidong
W
D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D019204:GTP-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation
D002352:Carrier Proteins; C469949:GNL3 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D019204:GTP-Binding Proteins