Over-expression of FRZB in gastric cancer cell suppresses proliferation and induces differentiation.
OBJECTIVE
Frizzled motif associated with bone development (FRZB) was a member of secreted frizzled related proteins (sFRPs) family. Previous evidences showed that FRZB played role in embryogenesis and diseases such as osteoarthritis and prostate cancer. The purpose of our study is to clarify the role of FRZB in gastric cancer cell proliferation and differentiation.


METHODS
The expression of FRZB in gastric cancer tissues were detected by immunohistochemistry. The expression of FRZB in eight gastric cancer cell lines and one immortal gastric epithelial cell GES-1 were detected by western blotting and real-time quantitative PCR. To investigate the role of over-expressed FRZB in gastric cancer cells, FRZB/pcDNA3.1 plasmid was constructed and transfected into gastric cancer cell line SGC7901. The changes of biological features in these stable transfectants were examined.


RESULTS
FRZB was highly expressed in gastric cancer (90%), intestinal metaplasia (100%) and gastric dysplasia (90%), but no or just weakly (3/40) expressed in normal gastric mucosa. FRZB staining was stronger in intestinal-type gastric cancer tissues than that in diffuse-type ones and was positive correlated with differentiation grade. The expression of FRZB in eight gastric cancer cell lines was higher than in GES-1. Over-expressed FRZB inhibited cell proliferation in vitro and in vivo which was first caused by prolonged cell division progression in G2/M phase, and second by higher sensitivity to apoptotic inducing factors and spontaneous apoptosis. Our findings gave evidences that FRZB suppressed gastric cancer cell proliferation and modulated the balance between proliferation and differentiation in gastric cancer.
Qu
Ying
Y
Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, 197 Rui Jin er Road, Shanghai 200025, China.
Li
Jian-Fang
JF
Cai
Qu
Q
Wang
Yun-Wei
YW
Gu
Qin-Long
QL
Zhu
Zheng-Gang
ZG
Liu
Bing-Ya
BY
D017209:Apoptosis; D002454:Cell Differentiation; D002455:Cell Division; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D016195:G2 Phase; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D014162:Transfection; D000099274:Frizzled-Related Proteins
D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D000099274:Frizzled-Related Proteins