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佛波酯诱导培养的人巨核母细胞分化过程中的基因表达。

Gene expression during phorbol ester-induced differentiation of cultured human megakaryoblastic cells.

作者信息

Dorn G W, Davis M G, D'Angelo D D

机构信息

Department of Internal Medicine, University of Cincinnati, Ohio 45267-0542.

出版信息

Am J Physiol. 1994 May;266(5 Pt 1):C1231-9. doi: 10.1152/ajpcell.1994.266.5.C1231.

DOI:10.1152/ajpcell.1994.266.5.C1231
PMID:8203487
Abstract

Platelet protein makeup is determined during transformation of megakaryoblasts to mature megakaryocytes, the immediate precursor of circulating platelets. To better understand the molecular mechanisms of megakaryocyte formation, gene expression was characterized by Northern analysis and RNA fingerprinting of cultured human CHRF-288 megakaryoblastic cells undergoing phorbol ester-stimulated megakaryocytic differentiation or serum-stimulated megakaryoblast proliferation. Protooncogenes c-fos and c-jun were coordinately upregulated in both proliferating and differentiating cells, whereas c-myc transcripts were upregulated during proliferation only. In contrast, mRNAs for transforming growth factor-beta 1 (TGF-beta 1) and thromboxane receptors were coordinately upregulated during differentiation but differentially regulated during proliferation. RNA fingerprinting revealed multiple transcripts specific to either proliferating or differentiated cells. Three of these were identified by homology to known DNA sequence: CDw44 adhesion molecule (upregulated during differentiation), glutathione sulfhydryl peroxidase (downregulated during differentiation), and plectin cytoskeletal protein (upregulated during differentiation). Thus, although megakaryoblast proliferation and megakaryocyte differentiation both involve DNA and protein synthesis, each growth response is characterized by a distinct pattern of gene expression.

摘要

血小板的蛋白质组成是在巨核母细胞向成熟巨核细胞(循环血小板的直接前体)转变的过程中确定的。为了更好地理解巨核细胞形成的分子机制,通过Northern分析和RNA指纹图谱对经佛波酯刺激发生巨核细胞分化或经血清刺激发生巨核母细胞增殖的培养人CHRF - 288巨核母细胞的基因表达进行了表征。原癌基因c - fos和c - jun在增殖细胞和分化细胞中均协同上调,而c - myc转录本仅在增殖过程中上调。相反,转化生长因子 - β1(TGF - β1)和血栓素受体的mRNA在分化过程中协同上调,但在增殖过程中受到不同调节。RNA指纹图谱揭示了增殖细胞或分化细胞特有的多种转录本。其中三种通过与已知DNA序列的同源性得以鉴定:CDw44黏附分子(在分化过程中上调)、谷胱甘肽巯基过氧化物酶(在分化过程中下调)和网蛋白细胞骨架蛋白(在分化过程中上调)。因此,尽管巨核母细胞增殖和巨核细胞分化都涉及DNA和蛋白质合成,但每种生长反应都具有独特的基因表达模式。

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