Gao Jie, Sai Ningning, Wang Chengqin, Sheng Xiehuang, Shao Qianqian, Zhou Chengjun, Shi Yanqiu, Sun Shanzhen, Qu Xun, Zhu Changjun
College of Life Science/Tianjin Key Laboratory of Cyto-Genetical and Molecular Regulation, Tianjin Normal University, Tianjin 300387, China.
Tumour Biol. 2011 Feb;32(1):53-61. doi: 10.1007/s13277-010-0090-0. Epub 2010 Aug 14.
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.
胃癌是一种常见的恶性肿瘤类型，且死亡率较高。胃癌的发病机制仍不清楚，越来越多的证据表明许多因素参与了这一过程。染色体驱动蛋白KIF4参与多个关键的细胞过程。最近，KIF4在肿瘤发生中发挥关键抑制作用已变得明显。然而，KIF4在人类胃癌中的作用仍不清楚。在本研究中，我们检测了KIF4在胃癌标本中的表达谱，并构建了稳定表达GFP-KIF4融合蛋白的胃癌细胞（命名为BGC-GFP-KIF4细胞），随后进行细胞增殖、3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐和软琼脂集落形成试验。同时，我们进一步检测了BGC-GFP-KIF4细胞在裸鼠体内的成瘤能力。结果显示，在23例胃癌标本中，13例（56.6%）与相应的癌旁组织相比KIF4表达较低。此外，KIF4低表达与肿瘤低分化之间存在显著相关性（P = 0.024）。在BGC细胞中过表达KIF4可抑制其体外细胞增殖以及体内成瘤能力。我们的研究结果表明，人类染色体驱动蛋白KIF4作为胃癌细胞增殖的抑制剂，可能成为治疗人类胃癌的新型生物学靶点。
