The inhibitory effect of aryl hydrocarbon receptor repressor (AhRR) on the growth of human breast cancer MCF-7 cells
The inhibitory effect of aryl hydrocarbon receptor repressor (AhRR) on the growth of human breast cancer MCF-7 cells
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DOI：
10.1248/bpb.29.1254
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发表时间：
2006-06-01
影响因子：
2
通讯作者：
Inouye, Yoshio
中科院分区：
文献类型：
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作者：
Kanno, Yuichiro;Takane, Yusuke;Inouye, Yoshio
从人乳腺癌MCF-7细胞中筛选出稳定表达AHRR的变异细胞系MCFRR1和MCFRR4，分析AHRR对细胞生长和细胞周期相关基因表达的影响。与亲本细胞相比，变异细胞表现出更高的AHRR mRNA水平。MTS法检测MCFRR4细胞生长速度和增殖速度均低于MCF-7细胞。在细胞周期相关基因E2F、细胞周期蛋白D1、增殖细胞核抗原、p53、Rb、c-myc和p27(Kip1)以及雌激素反应基因如组织蛋白D和热休克蛋白27中，MCFRR4细胞中E2F、细胞周期蛋白E1、增殖细胞核抗原和组织蛋白D基因的表达水平低于MCF-7细胞，而Rb、p27(Kip1)、c-myc和Hsp27基因的表达水平在变异细胞中无明显影响，而细胞周期蛋白D1mRNA的表达水平在变异细胞中增强。根据这些结果，AHRR可能通过干扰雌激素反应基因和细胞周期相关基因的转录和/或转录后调控来抑制MCF-7细胞的生长。
The variant cell lines stably expressing aryl hydrocarbon receptor repressor (AhRR), MCFRR1 and MCFRR4, were established from human breast cancer MCF-7 cells by transfecting with AhRR-expression construct followed by selection, in order to analyze the effect of AhRR on the cell growth and expression of cell cycle-related genes. The variant cells showed higher levels of AhRR mRNA compared with the parental cells. MCFRR4 cells grew slowly compared with MCF-7 in both cell number and proliferation rate measured by the MTS method. Among cell cycle-related genes such as E2F cyclin E1, cyclin D1, PCNA, p53, Rb, c-myc and p27(Kip1), and estrogen responsive genes such as cathepsin D and hsp27, the expression levels of E2F, cyclin E1, PCNA and cathepsin D mRNA in MCFRR4 cells were lower than those in MCF-7 cells, while those of Rb, p27(Kip1), c-myc and hsp27 mRNA were not significantly affected and that of cyclin D1 mRNA was enhanced in variant cells. Based on these results, AhRR might be suppressive on cell growth of MCF-7 by disturbing the transcriptional and/or posttranscriptional regulations of estrogen-responsive and cell cycle-related genes.