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HBP1过表达对白血病髓系细胞生长和分化的影响。

Effects of overexpression of HBP1 upon growth and differentiation of leukemic myeloid cells.

作者信息

Yao C J, Works K, Romagnoli P A, Austin G E

机构信息

Department of Pathology and Laboratory Medicine, Veterans Affairs Medical Center, Decatur, GA 30033, USA.

出版信息

Leukemia. 2005 Nov;19(11):1958-68. doi: 10.1038/sj.leu.2403918.

Abstract

HMG-box containing protein 1 (HBP1) is a member of the high mobility group (HMG) of chromosomal proteins. Since HBP1 exhibits tumor-suppressor activity in nonmyeloid tissues, we examined the effects of ectopic overexpression of HBP1 upon the growth and differentiation of myeloid cells. We prepared transient and stable transfectants of the myeloblast cell line K562, which overexpress HBP1 mRNA and protein. HBP1 transfectants displayed slower growth in cell culture and reduced colony formation in soft agar, retardation of S-phase progression, reduced expression of cyclin D1 and D3 mRNAs and increased expression of p21 mRNA. HBP1 transfectants also underwent increased apoptosis, as demonstrated by morphology and binding of Annexin V. Fas ligand mRNA levels were increased in HBP1 transfectants, suggesting involvement of the Fas/Fas ligand pathway. HBP1 overexpression enhanced differentiation of K562 cells towards erythroid and megakaryocyte lineages, as evidenced by increased hemoglobin and CD41a expression. Overexpression of HBP1 modulated mRNA levels for myeloid-specific transcription factors C/EBPalpha, c-Myb, c-Myc, and JunB, as well as lineage-specific transcription factors PU.1, GATA-1, and RUNX1. These findings suggest that in myeloid cells HBP1 may serve as a tumor suppressor and a general differentiation inducer and may synergize with chemical differentiating agents to enhance lineage-specific differentiation.

摘要

含HMG盒蛋白1(HBP1)是染色体蛋白高迁移率族(HMG)的成员之一。由于HBP1在非髓系组织中表现出肿瘤抑制活性,我们研究了HBP1异位过表达对髓系细胞生长和分化的影响。我们制备了过表达HBP1 mRNA和蛋白的成髓细胞系K562的瞬时和稳定转染子。HBP1转染子在细胞培养中生长较慢,在软琼脂中的集落形成减少,S期进程延迟,细胞周期蛋白D1和D3 mRNA表达降低,p21 mRNA表达增加。HBP1转染子的凋亡也增加,这通过形态学和膜联蛋白V结合得以证明。HBP1转染子中Fas配体mRNA水平增加,提示Fas/Fas配体途径参与其中。HBP1过表达增强了K562细胞向红系和巨核细胞系的分化,血红蛋白和CD41a表达增加证明了这一点。HBP1的过表达调节了髓系特异性转录因子C/EBPα、c-Myb、c-Myc和JunB以及谱系特异性转录因子PU.1、GATA-1和RUNX1的mRNA水平。这些发现表明,在髓系细胞中,HBP1可能作为一种肿瘤抑制因子和一般分化诱导剂,并可能与化学分化剂协同作用以增强谱系特异性分化。

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