Increased expression of cellular repressor of E1A-stimulated gene (CREG) in gastric cancer patients: a mechanism of proliferation and metastasis in cancer.
BACKGROUND
The cellular repressor of E1A-stimulated genes (CREG), a secreted glycoprotein, has been studied with human embryonic carcinoma cells, vascular smooth muscle cells, and NIH3T3 fibroblasts. However, its relationship to tumor cell proliferation and metastasis has not been examined in human gastric cancers (GC) until now.


OBJECTIVE
To investigate the expression of CREG in GC and its association with GC cell proliferation and metastasis.


METHODS
Forty-two cases of GCs, matched normal gastric tissues, and the human gastric cancer cell lines BGC-823, SGC-7901, MKN45, normal gastric mucosa cell line GES, and HUVEC cell line ECV304 were used to analyze CREG expression at the level of mRNA and protein. The expression of CREG was then further examined by immunohistochemistry in 42 GC tissues, and the correlation between the level of CREG and the pathological and clinical data was evaluated. Finally, we down-regulated the expression of CREG in GC cells with specific siRNA, and assessed the role of CREG in the proliferation and metastasis/invasion of the GC cell line.


RESULTS
The level of CREG was found to be higher in malignant GC tissues and cells compared to adjacent normal tissues and normal gastric cells (p < 0.001). Additionally, the expression levels of CREG were positively correlated with tumor clinical stage (p = 0.001), tumor metastasis (p < 0.001), and stages of tumor infiltration (p = 0.019). Furthermore, by using siRNA, we found that the down-regulated expression of CREG inhibited the proliferation of GC cells (p < 0.05), and migration of both GC cells (p = 0.001).


CONCLUSIONS
Our data suggest that CREG plays an important role in gastric cancer cell proliferation and metastasis and that CREG may be a potential therapeutic target for GC.
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 200072 Shanghai, China.
Ling
L
Xu
Feng
F
Wang
Hua
H
Liu
Xuan-Fu
XF
Xu
Wen-Hui
WH
Mo
Yu-Jing
YJ
Xia
Rong
R
Wan
Xing-Peng
XP
Wang
Chuan-Yong
CY
Guo
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000145:classification / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
C114068:CREG1 protein, human; D012097:Repressor Proteins