过表达CT120B基因诱导肺腺癌细胞G_1期停滞及基因表达谱改变  

The effects of CT120B over-expression on growth suppression and changes of gene expression profiles in lung adenocarcinoma cells

作　　者：潘东宁[1] 魏霖[1] 姚明[1] 万大方[1] 顾健人[1] 

机构地区：[1]上海市肿瘤研究所癌基因及相关基因国家重点实验室,200032

出　　处：《中华肿瘤杂志》2006年第5期321-325,共5页Chinese Journal of Oncology

基　　金：国家重点基础研究发展规划资助项目(2004CB518704)

摘　　要：目的探讨过表达CT120B基因对肺腺癌细胞生长的影响及其诱导的基因表达谱改变。方法用cDNA转染方法建立稳定过表达CT120B细胞株;CCK-8方法和裸鼠致瘤实验观察过表达CT120B对细胞在体外和体内生长的影响;表达阵列分析显示过表达CT120B诱导的基因表达谱变化;流式细胞仪检测细胞周期分布和细胞凋亡。结果过表达CT120B的SPC-A-1细胞株生长速度明显减慢,在裸鼠体内致瘤能力降低。在稳定过表达CT120B的细胞中,cyclin E1、cdk 2、c-kit和 CXCR4等34个基因表达下调,caspase 8等4个基因表达上调。过表达CT120B诱导细胞G1期停滞, 对细胞凋亡无明显影响。结论过表达CT120B通过诱导G1期停滞抑制肺腺癌细胞生长,稳定过表达CT120B细胞株中,c-kit和CXCR4等基因表达下调也有助于CT120B的生长抑制活性。Objective CT120B gene is a splicing variant of CT120A, which deletes 96 nucleotides and leads to an in-frame loss of 32 amino acids between the codon 136 and 167 as compared with CT120A. This study was undertaken to assess the effects of CT120B expression on lung cancer cell growth and to explore the gene expression profiles. Methods CT120B cDNA was transfected into the human lung adenocarcinoma SPC-A-1 ceils, and stable cell lines overexpressing CT120B were established. CCK-8 assay and tumorigenecity in a xenograft model were performed to analyze cell proliferation in vitro and in vivo. The differential gene expression induced by overexpressed CT120B was investigated using Atlas cDNA expression array. Flow cytometry was performed to analyze cell cycle and cell apoptosis. Results Overexpression of CT120B in SPC-A-1 cells resulted in a reduced cell growth rate in vitro, and decrease of the tumorigenicity in nude mice. A total of 38 genes were identified as differential expressions with more than a 2.0-fold change by Atlas cDNA expression array analysis, including downregulated cyclin E1, cdk 2, c-kit, CXCR4 and upregulated caspase 8 gene. Overexpression of CT120B also induced G1 phase arrest, but had no effect on cell apoptosis. Condusion The G1 cell cycle arrest, but not apoptosis, underlay the growth inhibitory activities of CT120B. The down-regulation of c-kit and CXCR4 expression might also contribute to the suppressive effects on cell growth of CT120B.

关 键 词：CT120B cDNA表达阵列 生长抑制 肺肿瘤 基因表达谱 

分 类 号：R734.2[医药卫生—肿瘤]