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.

已知多种生长因子可刺激造血细胞的分化和增殖。其中，最近克隆了人粒细胞集落刺激因子（G-CSF）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）的cDNA，并确定了其一级结构。为了阐明这些因素在正常和转化造血中的可能作用，我们进行了以下实验。首先，通过Northern杂交检测了血液恶性肿瘤或实体瘤的几个临床样本中GM-CSF和G-CSF的表达。 1 例胶质母细胞瘤、2 例肺癌和 1 例成人 T 细胞白血病 (ATL) 病例均表达 GM-CSF mRNA。细胞系由一种胶质母细胞瘤和一种肺癌开发而来，并被发现在其培养上清液中分泌 GM-CSF 活性。因此，建议将这些 GM-CSF 转录物翻译成 GM-CSF 蛋白。这是关于实体瘤中GM-CSF表达的第一份报告。 G-CSF被发现在3例肺癌和1例肝细胞癌病例中表达。在1例肺癌病例中，mRMA的大小与正常情况不同。其次，为了研究G-CSF对体内细胞的作用，我们给Bald/c小鼠皮下注射重组人G-CSF（rhG-CSF）两周。在注射小鼠中观察到肥大的肝脏和脾脏。从这些器官中提取RNA，并通过Northern杂交与几种酪氨酸激酶癌基因探针进行低严格性检查。我们发现与 fps 基因同源但不同的转录物，与对照肝脏相比，在肥大肝脏中表达增加。