Characterization of the expression of HTm4 (MS4A3), a cell cycle regulator, in human peripheral blood cells and normal and malignant tissues.

Characterization of the expression of HTm4 (MS4A3), a cell cycle regulator, in human peripheral blood cells and normal and malignant tissues.
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人类外周血细胞以及正常和恶性组织中细胞周期调节剂 HTm4 (MS4A3) 表达的表征。

DOI:
10.1111/j.1582-4934.2009.00925.x
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发表时间:
2011-01
影响因子:
5.3
通讯作者:
Adra CN
Adra CN
中科院分区:
医学2区
文献类型:
--
作者:
Kutok JL;Yang X;Folkerth R;Adra CN

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HTm4 (MS4A3) 是称为 MS4A 的四次跨膜蛋白家族的成员。 MS4A 蛋白履行多种功能,充当细胞表面信号分子和细胞内衔接蛋白。早期报告表明,HTm4 在很大程度上局限于造血谱系,并通过与激酶相关磷酸酶、细胞周期蛋白 A 和细胞周期蛋白依赖性激酶 2 (CDK2) 的调节相互作用参与细胞周期控制。在这里,我们使用基因表达微阵列技术描述了外周血细胞中HTm4的表达模式,并使用组织微阵列技术描述了正常胎儿和成人组织以及成人癌症中HTm4的表达模式。使用寡核苷酸微阵列评估 HTm4 mRNA,所有外周血细胞类型均表现出非常低水平的 HTm4 表达;然而,与嗜酸性粒细胞相比,HTm4 在嗜碱性粒细胞中的表达最高,而嗜酸性粒细胞的 HTm4 表达水平较低。通过谱系特异性造血细胞流式细胞术分析,在单核细胞、粒细胞和 B 细胞中发现非常弱的 HTm4 表达,但在 T 细胞中没有发现。有趣的是,植物血凝素刺激使外周血 CD4-T 淋巴细胞中 HTm4 蛋白的表达增加到几乎不可检测的基线水平。蛋白质印迹和免疫组织化学研究表明,人类胎儿肝脏发育中的造血细胞中有强烈的 HTm4 表达。对正常组织微阵列的免疫组织化学研究证实,在结节、脾组织和胸腺组织的白细胞亚群中存在 HTm4 表达,并且在非造血组织中的少数细胞类型中存在弱染色。妊娠 19 至 31 周的人类胎儿大脑样本显示,染色最强的细胞是心室区细胞和皮质板中最早出生、最早分化的“先锋”神经元 Cajal-Retzius,以及较小程度的亚板样神经元。恶性组织微阵列分析显示 HTm4 在多种腺癌中表达,包括乳腺癌、前列腺癌和卵巢癌。这些发现值得进一步研究 HTm4 在造血细胞和肿瘤细胞的细胞周期中的作用。
HTm4 (MS4A3) is a member of a family of four-transmembrane proteins designated MS4A. MS4A proteins fulfil diverse functions, acting as cell surface signalling molecules and intracellular adapter proteins. Early reports demonstrated that HTm4 is largely restricted to the haematopoietic lineage, and is involved in cell cycle control, via a regulatory interaction with the kinase-associated phosphatase, cyclin A and cyclin-dependent kinase 2 (CDK2). Here we describe the expression pattern of HTm4 in peripheral blood cells using gene expression microarray technology, and in normal foetal and adult human tissues, as well as adult human cancers, using tissue microarray technology. Using oligonucleotide microarrays to evaluate HTm4 mRNA, all peripheral blood cell types demonstrated very low levels of HTm4 expression; however, HTm4 expression was greatest in basophils compared to eosinophils, which showed lower levels of HTm4 expression. Very weak HTm4 expression is found in monocytes, granulocytes and B cells, but not in T cells, by lineage specific haematopoietic cell flow cytometry analysis. Interestingly, phytohaemagglutinin stimulation increases HTm4 protein expression in peripheral blood CD4-T-lymphocytes over nearly undetectable baseline levels. Western blotting and immunohistochemical studies show strong HTm4 expression in the developing haematopoietic cells of human foetal liver. Immunohistochemical studies on normal tissue microarrays confirmed HTm4 expression in a subset of leucocytes in nodal, splenic tissues and thymic tissue, and weak staining in small numbers of cell types in non-haematopoietic tissues. Human foetal brain specimens from 19 to 31 gestational weeks showed that the strongest-staining cells are ventricular zone cells and the earliest-born, earliest-differentiating ‘pioneer’ neurons in the cortical plate, Cajal-Retzius and, to a lesser extent, subplate-like neurons. Malignant tissue microarray analysis showed HTm4 expression in a wide variety of adenocarcinomas, including breast, prostate and ovarian. These findings warrant the further study of the role of HTm4 in the cell cycle of both haematopoietic and tumour cells.
DOI: 10.1034/j.1399-0004.1999.550606.x
发表时间: 1999-06-01
期刊: CLINICAL GENETICS
影响因子: 3.5
作者:
Adra, CN;Mao, XQ;Hopkin, JM
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期刊: IMMUNOGENETICS
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发表时间: 1988-01-01
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发表时间: 2004-03-01
影响因子: 14.2
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