Bodey B, Bodey B, Siegel S E, Kaiser H E
Department of Pathology, University of Southern California, Los Angeles, USA.
In Vivo. 2000 May-Jun;14(3):419-24.
The homeobox (HOX) was originally described as a conserved DNA motif of about 180 base pairs. The protein domain encoded by the homeobox, the homeodomain, is thus about 60 amino acids long. The homeodomain is a DNA-binding domain, and many homeobox genes have now been shown to bind to DNA and regulate the transcription of other genes. Thus homeodomain proteins are basically transcription factors, most of which play a role in development. The homeobox genes seem to represent another class of oncofetal antigens involved in both normal development and carcinogenesis, as well as tumor progression. The expression pattern of three homeobox gene products (HOX-B3, HOX-B4, and HOX-C6) was examined immunocytochemically in human thymuses of different ages and developmental stages (prenatal: 16 weeks and postnatal: 3 years, 5 years, and 21 years) employing an indirect alkaline phosphatase conjugated antigen detection technique on formalin-fixed, paraffin-embedded tissue sections. The immunoreactivity was located in the thymic RE cellular network (cortical and medullar), showing different intensity (+3 to +4 or 50% to 90% and over 90% in the prenatal thymic tissue and +2 to +3 or 50% to 90% during the three different postnatal stages). Intense expression was identified in the thymic medulla, including very strong immunoreactivity in the immigrating, committed hematopoietic stem cells (HSCs) present within the interlobular connective tissue (ICT). Strong presence of the HOX-B3 and HOX-B4 proteins was detected in the thymic Hassall's bodies (HBs), suggesting an intensive functional activity of the RE cells present within these unique formations within the thymic medulla. The precise role of these and other HOX gene products in the various steps of intrathymic T lymphopoieis should be elucidated through further basic molecular biological research.
同源框(HOX)最初被描述为一个约180个碱基对的保守DNA基序。因此,由同源框编码的蛋白质结构域——同源结构域,大约有60个氨基酸长。同源结构域是一个DNA结合结构域,现在已经证明许多同源框基因能与DNA结合并调节其他基因的转录。因此,同源结构域蛋白基本上是转录因子,其中大多数在发育过程中发挥作用。同源框基因似乎代表了另一类癌胚抗原,参与正常发育、致癌作用以及肿瘤进展。采用间接碱性磷酸酶偶联抗原检测技术,在福尔马林固定、石蜡包埋的组织切片上,对不同年龄和发育阶段(产前:16周,产后:3岁、5岁和21岁)的人胸腺进行免疫细胞化学检测,观察三种同源框基因产物(HOX - B3、HOX - B4和HOX - C6)的表达模式。免疫反应性定位于胸腺网状细胞网络(皮质和髓质),显示出不同的强度(产前胸腺组织中为+3至+4或50%至90%以及超过90%,产后三个不同阶段为+2至+3或50%至90%)。在胸腺髓质中发现了强烈表达,包括在小叶间结缔组织(ICT)中存在的迁移性、定向造血干细胞(HSCs)中有非常强的免疫反应性。在胸腺哈氏小体(HBs)中检测到HOX - B3和HOX - B4蛋白的强烈存在,表明在胸腺髓质内这些独特结构中存在的网状细胞具有强烈的功能活性。这些以及其他HOX基因产物在胸腺内T淋巴细胞生成各个步骤中的精确作用,应通过进一步的基础分子生物学研究来阐明。