Analysis of normal hematopoiesis and leukemogenesis using hematopoietic growth factor genes.

使用造血生长因子基因分析正常造血和白血病发生。

基本信息

批准号：
62570536
负责人：
ISHIKAWA Fuyuki
金额：
$ 1.15万
依托单位：
University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570536/
关键词：
Hematopoiesis G-CSF GM-CSF 造血ノーザンブロッテイングヒト固形腫瘍

项目摘要

Several growth factors are known to stimulate the differentiation and proliferation of hematopoietic cells. Among them, recently, cDNAs of human granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were cloned and the primary structures were determined. To clarify the possible roles of these factors in normal and transformed hematopoiesis, we undertook the following experiments. Firstly, several clinical samples of either hematological malignancies or solid tumors were tested about their expression of GM-CSF and G-CSF by northern hybridization. One glioblastoma, two lung cancers and one adult T cell leukemia (ATL) cases were shown to express GM-CSF mRNA. Cell lines were developed from one glioblastoma and one lung cancer and were found to secrete GM-CSF activity in their culture supernatants. Thus, these GM-CSF transcripts were suggested to be translated into GM-CSF proteins. This is the first report about the expression of GM-CSF in solid tumors. G-CSF was found to be expressed in three lung cancers and one hepatocellular carcinoma cases.In one case of lung cancer, the size of the mRMA was different from that seen normally. Secondly, to investigate the action of G-CSF to cells in vivo, we injected recombinant human G-CSF (rhG-CSF) to Bald/c mice subcutaneously for two weeks. Hypertrophic liver and spleen were observed in injected mice. RNAs were extracted from these organs and examined at low stringency by Northern hybridization with several tyrosine kinase oncogene probes. We found a transcript homologous with but distinct from fps gene, was increasedly expressed in hypertrophic liver compared to control liver.

已知几种生长因子刺激造血细胞的分化和增殖。最近，将人粒细胞刺激因子（G-CSF）和粒细胞巨噬细胞刺激性刺激因子（GM-CSF）的cDNA克隆，并确定主要结构。为了阐明这些因素在正常和转化的造血中的可能作用，我们进行了以下实验。首先，通过北部杂交测试了血液系统恶性肿瘤或实体瘤的几种临床样本。一种胶质母细胞瘤，两个肺癌和一个成年T细胞白血病（ATL）病例显示出表达GM-CSF mRNA。细胞系是由一种胶质母细胞瘤和一个肺癌开发的，并被发现分泌其培养上清液中的GM-CSF活性。因此，建议将这些GM-CSF转录本转化为GM-CSF蛋白。这是关于GM-CSF在实体瘤中表达的第一个报告。发现G-CSF在三种肺癌和一个肝细胞癌病例中表达。在一种肺癌中，MRMA的大小与正常情况下的大小不同。其次，为了研究G-CSF对体内细胞的作用，我们将重组人G-CSF（RHG-CSF）注射到秃头/C小鼠中，持续了两个星期。在注射小鼠中观察到肥厚的肝脏和脾脏。从这些器官中提取RNA，并通过北部杂交与几个酪氨酸激酶癌基因探针进行北部杂交。我们发现与对照肝脏相比，在肥厚性肝脏中增加了具有不同但与FPS基因不同的转录本同源物。