Overexpression of chromokinesin KIF4 inhibits proliferation of human gastric carcinoma cells both in vitro and in vivo.
Gastric carcinoma is a common type of malignant tumors and is associated with high death rates. The pathogenesis of gastric carcinoma is still unclear, and increasing evidence shows that many factors contribute to this process. Chromokinesin KIF4 is involved in multiple critical cellular processes. Recently, it has become apparent that KIF4 plays a crucial suppressive role in tumorigenesis. However, the role of KIF4 in human gastric cancer is still unclear. In this study, we examined expression profiles of KIF4 in gastric carcinoma specimens and generated gastric cancer cells that stably express GFP-KIF4 fusion protein (designated as BGC-GFP-KIF4 cells) followed by cell proliferation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and soft agar colony-formation assays. Simultaneously, we further examined the capability of tumor formation of BGC-GFP-KIF4 cells in nude mice. The results showed that among 23 gastric carcinoma specimens, 13 cases (56.6%) had lower expression of KIF4 compared with corresponding adjacent tissues. In addition, there was a significant correlation between low expression of KIF4 and poor differentiation of tumor (P = 0.024). Overexpression of KIF4 in BGC cells inhibited cell proliferation in vitro, as well as their ability to form tumors in vivo. Our findings suggest that human chromokinesin KIF4 functions as an inhibitor of gastric cancer cell proliferation and might serve as a novel biological target to cure human gastric carcinoma.
Gao
Jie
J
College of Life Science/Tianjin Key Laboratory of Cyto-Genetical and Molecular Regulation, Tianjin Normal University, Tianjin 300387, China.
Sai
Ningning
N
Wang
Chengqin
C
Sheng
Xiehuang
X
Shao
Qianqian
Q
Zhou
Chengjun
C
Shi
Yanqiu
Y
Sun
Shanzhen
S
Qu
Xun
X
Zhu
Changjun
C
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D005455:Fluorescent Antibody Technique; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D016547:Kinesins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011379:Prognosis; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D015996:Survival Rate; D023041:Xenograft Model Antitumor Assays
C484228:KIF4A protein, human; C089655:Kif4 protein, mouse; D016547:Kinesins