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一种生长抑制性三肽,乙酰基谷氨酰胺-丝氨酸-甘氨酰胺(Ac-ESG),对两种淋巴瘤细胞系基因表达和细胞周期进程的影响。

The effects of a growth-inhibiting tripeptide, acetylGlu-Ser-GlyNH2 (Ac-ESG), on gene expression and cell cycle progression of two lymphoma cell lines.

作者信息

Liu Ying, Reichelt Wenche H, Luna Luisa, Elgjo Kjell, Reichelt Karl L

机构信息

Institute of Pediatric Research, National Hospital, University of Oslo, N-0027 Oslo, Norway.

出版信息

Anticancer Res. 2003 Jul-Aug;23(4):3159-65.

Abstract

BACKGROUND

We recently isolated and characterized a tripeptide, acetylGlu-Ser-GlyNH2 (Ac-ESG), which inhibits proliferation of lymphoid cells. In this paper we describe the effects of Ac-ESG on growth-related gene expression and cell cycle progression in two lymphoma cell lines, Ramos and Molt, representing B and T lymphocytes, respectively.

MATERIALS AND METHODS

RNA was extracted from Molt and Ramos cells with or without the tripeptide treatment. Gene expression was examined by semi-quantitative RT-PCR and Northern blot hybridization, and cell cycle progression was detected by flow cytometry.

RESULTS

In the Molt cells, p53 gene expression was increased following treatment while c-myc was decreased after treatment shorter than 24 hours; N-ras expression was significantly reduced at picomolar concentration for 24-hour treatment; cyclinD1 and cdk4 expression did not show any change; DNA flow cytometry demonstrated that Molt cells were arrested or delayed predominantly in G2-M. Untreated Ramos cells had higher gene expression levels of c-myc, N-Ras and cdk4 than Molt cells, but lower p53 expression. These cells were not sensitive to Ac-ESG.

CONCLUSION

The tripeptide Ac-ESG alters the expression of several growth-related genes in the Molt cell line and brings about an arrest or delay of cells in G2-M.

摘要

背景

我们最近分离并鉴定了一种三肽,乙酰谷氨酸-丝氨酸-甘氨酰胺(Ac-ESG),它能抑制淋巴细胞的增殖。在本文中,我们描述了Ac-ESG对分别代表B淋巴细胞和T淋巴细胞的两种淋巴瘤细胞系Ramos和Molt中与生长相关基因表达和细胞周期进程的影响。

材料与方法

从经或未经三肽处理的Molt和Ramos细胞中提取RNA。通过半定量逆转录聚合酶链反应(RT-PCR)和Northern印迹杂交检测基因表达,通过流式细胞术检测细胞周期进程。

结果

在Molt细胞中,处理后p53基因表达增加,而处理少于24小时后c-myc表达降低;在皮摩尔浓度下处理24小时,N-ras表达显著降低;细胞周期蛋白D1(cyclinD1)和细胞周期蛋白依赖性激酶4(cdk4)表达未显示任何变化;DNA流式细胞术表明,Molt细胞主要停滞或延迟在G2-M期。未经处理的Ramos细胞中,c-myc、N-Ras和cdk4的基因表达水平高于Molt细胞,但p53表达较低。这些细胞对Ac-ESG不敏感。

结论

三肽Ac-ESG改变了Molt细胞系中几种与生长相关基因的表达,并导致细胞在G2-M期停滞或延迟。

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