A STUDY OF HTLV-1-RELATED DISEASES BY MEANS OF HIGHLY SENSITIVE HISTOCHEMISTRY

利用高灵敏组织化学方法研究 HTLV-1 相关疾病

基本信息

批准号：
10670166
负责人：
HASUI Kazuhisa
金额：
$ 2.05万
依托单位：
Kagoshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670166/
关键词：
Highly sensitive histochemistry HTLV-1 Tax Rex E2F Cyclin E ATLL T-cell lymphoma CyclinE T-cell Lymphoma

项目摘要

This study aimed to see pathogenesis of HTLV-1-related diseases, especially adult T-cell leukemia/lymphoma (ATLL) by means of highly-sensitive histochemistry. Integrated HTLV-1 proviral DNA is the first target to be detected by means of the highly-sensitive histochemistry. But, because of degradation of DNA strands in paraffon sections of routinely processed tissue, the proviral DNA is not a good target to be detected in the sections. We established highly sensitive immunohistochemistry of HTLV-1 p40Tax (Tax), p27Rex (REx), and transcription factors in G1/S transition of cell cycle. By means of the highly-sensitive immunohistochemistry, the relation of expression of Tax and Rex and to the phenotypic transformation in ATLL cells, and to the expression of the transcription factors in G1/S transition of cell cycle. ATLL cells expressed much more Rex than Tax. ATLL cells did not expressed Tax in all phases of cell growth and proliferation. Highly-sensitive histochemical detection of Tax and Rex is useful in the differential diagnosis of ATLL from the other T-cell lymphomas. ATLL cells showed overexpression of one of E2F families in nucleus or no expression of them, whereas European cases of T-cell lymphomas without HTLV-1 infection showed overexpression of cyclin E. Expressing a small amount of Tax, ATLL cells expressed weakly cyclin E in asmall number of nuclei. Consequently, it was suggested that HTLV-1 leukemogenesis of ATLL focuses on the proliferation signal transduction system that ends to release E2F from retinoblastoma protein to nucleus in G1/S transition. On the other hand, ATLL cells suggested over-riding checkpoint abnormality in cell cycle, expressing a large amount of E2F in nuclei even in S phase of cell cycle in some cases. Tax expressed weakly expressed in ATLL cells was thought to induce weak expression of cyclin E in nucleus, although this expression of cyclin E is thought to be a part of preserved cell function.

本研究旨在通过高灵敏的组织化学手段了解 HTLV-1 相关疾病的发病机制，特别是成人 T 细胞白血病/淋巴瘤 (ATLL)。整合的 HTLV-1 前病毒 DNA 是第一个通过高灵敏组织化学检测到的靶标。但是，由于常规处理的组织的石蜡切片中的 DNA 链会降解，因此前病毒 DNA 不是切片中检测的良好目标。我们建立了细胞周期 G1/S 转变中 HTLV-1 p40Tax (Tax)、p27Rex (REx) 和转录因子的高灵敏免疫组织化学方法。利用高灵敏的免疫组化方法，研究了ATLL细胞中Tax和Rex的表达与表型转变的关系，以及细胞周期G1/S转变中转录因子表达的关系。 ATLL 细胞表达的 Rex 多于 Tax。 ATLL细胞在细胞生长和增殖的所有阶段均不表达Tax。 Tax 和 Rex 的高灵敏组织化学检测可用于 ATLL 与其他 T 细胞淋巴瘤的鉴别诊断。 ATLL 细胞在细胞核中过度表达 E2F 家族之一或不表达，而欧洲未感染 HTLV-1 的 T 细胞淋巴瘤病例显示细胞周期蛋白 E 过度表达。 ATLL 细胞表达少量 Tax，在细胞中弱表达细胞周期蛋白 E。少量的原子核。因此，有人认为ATLL的HTLV-1白血病发生集中于增殖信号转导系统，该系统最终在G1/S转变期间将E2F从视网膜母细胞瘤蛋白释放到细胞核。另一方面，ATLL细胞表现出细胞周期中压倒性的检查点异常，在某些情况下甚至在细胞周期的S期细胞核中表达大量E2F。 ATLL细胞中弱表达的Tax被认为诱导细胞核中细胞周期蛋白E的弱表达，尽管细胞周期蛋白E的这种表达被认为是保留的细胞功能的一部分。