高表达Ck2β与大肠癌发生和转移的相关性研究

摘要

目的 探讨ck2β蛋白在正常大肠粘膜、大肠腺瘤和大肠癌组织中的表达及其在大肠癌发生及转移中的作用.方法 采用免疫组化方法检测46例正常大肠粘膜组织、20例大肠腺瘤及66例大肠癌组织中ck2β蛋白的表达.用RNA干扰技术沉默大肠癌细胞中ck2β蛋白表达,Western blot实验检测干扰效果;平板克隆形成实验检测细胞增殖能力的变化;Transwell侵袭小室实验检测细胞侵袭能力的变化.结果 ck2β在正常大肠粘膜组织中不表达或弱表达,核表达阳性率为8.7%,浆表达阳性率为13.0%;在大肠腺瘤组织中中度表达,60%呈核阳性表达,40%呈浆阳性表达;而在大肠癌组织中,ck2β呈强阳性表达,核表达阳性率为75.8%,浆表达阳性率为62.1%,三者间差异有统计学意义(P＜0.05).ck2β蛋白表达与大肠癌的淋巴结转移密切相关,伴发淋巴结转移的大肠癌组织ck2β阳性表达明显高于无淋巴结转移者(P＜0.05).体外实验发现,沉默大肠癌细胞中ck2β的表达能显著抑制细胞的增殖及侵袭能力.结论 ck2β蛋白的表达与大肠癌的发生和转移密切相关.%Objective To investigate the expression of casein kinase 2β (ck2β) in colorectal cancer in relation to the metastatic ability of the cancer cells. Methods The expression of ck2p in 46 normal colorectal mucosa, 20 colorectal adenomas and 66 colorectal cancers were detected immunohistochemically. In colorectal cancer cells, Ck2p protein expression was knockdowned by RNA interference using ck2p-specific small interfering RNA (siRNA) and the interference efficiency was assessed by Western blotting. The effect of ck2p gene knockdown on the proliferation of the colorectal cancer cells was tested with colony formation assay, and the changes in the invasive ability of the cells were observed using Transwell chamber assay. Results Negative or weak ck2p expression was detected in normal colorectal mucosa, with nuclear posihvity in 8.7% and cytoplasmic positivity in 13.0% of the cases. Colorectal adenomas showed moderate ck2p expression, with 60% cases showing positivity in the cell nuclei and 40% in the cytoplasm. In colorectal cancers, significantly stronger expression of ck2p was found than that in colorectal adenomas and normal colorectal mucosa (.(P＜0.05), and 75.8% cases showed positivity in the cell nuclei and 62.1% showed cytoplasmic positivity; the expression of ck2p protein in colorectal cancers with lymph node metastasis was even higher (P＜0.05). Ck2p knockdown obviously inhibited the proliferation and invasiveness of colorectal cancer cells in vitro. Conclusion The high expression of ck2β in colorectal cancer is closely correlated to the carcinogenesis and metastasis of the tumor.