Anti-epidermal growth factor receptor monoclonal antibody 225 upregulates p27KIP1 and p15INK4B and induces G1 arrest in oral squamous carcinoma cell lines
Anti-epidermal growth factor receptor monoclonal antibody 225 upregulates p27KIP1 and p15INK4B and induces G1 arrest in oral squamous carcinoma cell lines
复制标题
DOI：
10.1159/000065726
复制
发表时间：
2002-01-01
期刊：
影响因子：
3.5
通讯作者：
Wong, DTW
中科院分区：
文献类型：
--
作者：
Kiyota, A;Shintani, S;Wong, DTW
表皮生长因子受体（EGFR）调节人口腔鳞状细胞癌（SCC）的生长和进展。最近，EGFR信号传导和细胞周期之间的联系已被确定。一些报道描述了EGFR阻断单克隆抗体225（mAb225）诱导G1期阻滞并抑制各种癌细胞的生长。本研究的目的是评估mAb 225对人口腔鳞癌细胞系的作用。在培养物中暴露于mAb 225以与EGFR数量无关的方式抑制口腔SCC细胞系的生长，抑制百分比范围为13.8%至76.6%。流式细胞术分析表明，用mAb225处理诱导细胞在G1期积累，伴随着S期细胞百分比的降低。本研究中未观察到细胞凋亡。G1期阻滞伴随着CDK2、CDK4和CDK6相关组蛋白H1激酶活性的降低，以及细胞周期抑制剂p27（KIP1）和p15（INK4B）表达水平的增加。提示mAb225阻断EGFR对口腔鳞癌细胞增殖的抑制作用可能是通过p27（KIP 1）和P15（INK 4B）介导的。版权所有（C）2002 S. Karger AG，巴塞尔。
Epidermal growth factor receptor (EGFR) regulates the growth and progression of human oral squamous cell carcinoma (SCC). Recently, the link between EGFR signaling and the cell cycle has been identified. Some reports have described that EGFR-blocking monoclonal antibody 225 (mAb225) induced G1 arrest and inhibited the growth of various cancer cells. The purpose of this study was to evaluate the effect of mAb225 on human oral SCC cell lines. Exposure to mAb225 in culture inhibited the growth of oral SCC cell lines in an EGFR number-independent manner, with the percent inhibition ranging from 13.8 to 76.6%. Flow-cytometric analysis demonstrated that treatment with mAb225 induced cell accumulation in G1 phase, accompanied by a decrease in the percentage of cells in the S phase. Apoptosis was not seen in this study. G1 arrest was accompanied by a decrease in CDK2-, CDK4-, and CDK6-associated histone H1 kinase activities, and an increase in the expression levels of cell cycle inhibitors p27(KIP1) and p15(INK4B). These results suggested that the antiproliferative effect of EGFR blockade by mAb225 in oral SCC may be mediated by p27(KIP1) and P15(INK4B). Copyright (C) 2002 S. Karger AG, Basel.