ISOLATION OF NOVEL ONCOGENES BY AN EFFICIENT EXPRESSION CLONING SYSTEM

通过高效表达克隆系统分离新型癌基因

• 批准号: 5201509
• 负责人: T MIKI
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5201509
• 关键词: 3T3 cells; animal genetic material tag; athymic mouse; biological signal transduction; cell cycle proteins; cell differentiation; cell transformation; chromosomes; embryo /fetus cell /tissue; fibroblast growth factor; gene expression; genetic mapping; guanine nucleotide binding protein; human genetic material tag; human tissue; laboratory mouse; melanocyte; microphthalmos; molecular cloning; neoplastic transformation; oncogenes; oncoproteins; protein kinase; testis; transcription factor

Using an efficient expression cloning system, several novel oncogenes were isolated from various tissues and cell lines. By analyzing these oncogenes, signal transduction pathways for malignant transformation are being clarified. The main findings this year are as follows: (1) A transforming gene was isolated from mouse testis and found to encode a growth factor of the fibroblast growth factor family (FGF-8); and it is mainly expressed in embryonic tissues but not in adult tissue, except testis. The location of the human FGF-8 gene was mapped to chromosome 10. (2) A signal transduction pathway downstream from ost, an oncogene that was isolated using this system, was clarified. Ost activates a small GTP-binding protein, Cdc42, and in turn it activates a protein kinase cascade, stress-activated protein kinase (SAPK) or c-Jun amino- terminal kinase (JNK) pathway. (3) The chromosomal locations of ect2 and TIM, oncogenes that were isolated using this system previously, have been determined to be 3q26.1-q26.2 and 7q33-q35, respectively; where common chromosomal rearrangements were reported in human malignancies. (4) microphthalmia transcription factor (MITF), the human homolog of the mouse microphthalmia gene, was cloned. Ectopic expression of MITF in NIH/3T3 cells induced morphologically altered cells, but MITF transfectants did not induce tumors in nude mice. Interestingly, MITF- induced foci contain melanocyte-like cells with dendritic processes. These cells also expressed melanogenic markers, indicating that MITF is involved in melanocyte differentiation.

利用高效的表达克隆系统， 从各种组织和细胞系中分离。 通过分析这些 癌基因，恶性转化的信号转导途径， 正在澄清。 本年度的主要研究结果如下：（1）A 从小鼠睾丸中分离到一个转化基因， 成纤维细胞生长因子家族的生长因子（FGF-8）;并且 主要在胚胎组织中表达，但在成体组织中不表达， 睾丸 将人FGF-8基因定位于染色体上， 10. (2)癌基因ost下游的一条信号转导通路 用这个系统分离出来的，被澄清了。 Ost激活a 一种小的GTP结合蛋白Cdc 42，它反过来激活一种蛋白质 激酶级联、应激活化蛋白激酶（SAPK）或c-Jun氨基- 末端激酶（JNK）通路。 (3)ect 2的染色体定位 和TIM，以前使用该系统分离的癌基因， 分别为3q26.1-q26.2和7 q33-q35;其中 在人类恶性肿瘤中报道了常见的染色体重排。 (4)小眼症转录因子（MITF），人类同源物的 小鼠小眼畸形基因。 MITF的异位表达 NIH/3 T3细胞诱导细胞形态改变，但MITF 转染子在裸鼠中不诱导肿瘤。 有趣的是，MITF- 诱导的病灶含有具有树突状突起的黑素细胞样细胞。 这些细胞也表达黑素标记，表明MITF是 参与黑素细胞分化。