Zhou Y Q, Chen S L, Ju J Y, Shen L, Liu Y, Zhen S, Lv N, He Z G, Zhu L P
Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.
Cancer Sci. 2009 Oct;100(10):1817-22. doi: 10.1111/j.1349-7006.2009.01261.x. Epub 2009 Jun 24.
BCSC-1 is dramatically upregulated in CNE-2L2 human nasopharyngeal carcinoma cells with reduced malignancy (AS cells) and is proposed to be a candidate tumor suppressor gene. We therefore examined the effect of BCSC-1 expression on malignant behaviors of CNE-2L2 cells. Growth in vitro and tumorigenesis in nude mice of wild-type CNE-2L2 cells (W cells) were inhibited by ectopic BCSC-1, and those of AS cells were promoted by BCSC-1 suppression. The tumor suppressor function of BCSC-1 was further confirmed by a study showing that intratumor BCSC-1 injection caused growth suppression of the tumor from W cells inoculated in nude mice. Immunohistochemistry exhibited marked reduction of BCSC-1 expression in 11 of 39 human nasopharyngeal carcinoma specimens. Because BCSC-1 expression was as rich as that in normal cells in the rest of the carcinoma specimens and was poor in CNE-2L2 cells, HNE-1 human nasopharyngeal carcinoma cells with rich BCSC-1 expression were used as a control in the study. No effect of BCSC-1 transfection on growth of the cells was observed. The data suggest that BCSC-1 suppression might play roles in tumorigenesis of some nasopharyngeal carcinomas and that BCSC-1 might be a potential gene therapy target in nasopharyngeal carcinomas with poor BCSC-1 expression. Enhanced aggregation of cells together with increased E-cadherin and alpha-catenin expression and reduced Wnt signaling might be involved in the mechanisms of tumor suppressor function of BCSC-1.
BCSC-1在恶性程度降低的CNE-2L2人鼻咽癌细胞(AS细胞)中显著上调,被认为是一种候选肿瘤抑制基因。因此,我们研究了BCSC-1表达对CNE-2L2细胞恶性行为的影响。异位表达BCSC-1可抑制野生型CNE-2L2细胞(W细胞)的体外生长和裸鼠成瘤,而抑制BCSC-1可促进AS细胞的生长。一项研究进一步证实了BCSC-1的肿瘤抑制功能,该研究表明,向接种于裸鼠的W细胞肿瘤内注射BCSC-1可导致肿瘤生长受抑。免疫组化显示,在39例人鼻咽癌标本中,有11例BCSC-1表达明显降低。由于其余癌标本中BCSC-1表达与正常细胞一样丰富,而在CNE-2L2细胞中表达较弱,因此在研究中使用BCSC-1表达丰富的HNE-1人鼻咽癌细胞作为对照。未观察到BCSC-1转染对细胞生长有影响。数据表明,BCSC-1抑制可能在某些鼻咽癌的发生中起作用,并且BCSC-1可能是BCSC-1表达较弱的鼻咽癌潜在的基因治疗靶点。细胞聚集增强、E-钙黏蛋白和α-连环蛋白表达增加以及Wnt信号传导减少可能参与了BCSC-1肿瘤抑制功能的机制。