ORGANIZATION AND CONTROL OF GENETIC MATERIAL IN PLASMACYTOMAS

浆细胞瘤中遗传物质的组织和控制

• 批准号: 3963044
• 负责人: J F MUSHINSKI
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 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/3963044
• 关键词: Abelson leukemia virus; B lymphocyte; DNA; cell growth regulation; cellular oncology; cytogenetics; gene expression; genetic manipulation; genetic mapping; genetic transcription; human tissue; immunochemistry; immunoglobulin D; immunoglobulin M; immunoglobulin genes; liver; lymphocyte; lymphocytic leukemia; lymphoma; lymphosarcoma; membrane activity; messenger RNA; molecular cloning; molecular oncology; mouse leukemia; myelofibrosis; neoplasm /cancer genetics; neoplasm /cancer immunology; nucleic acid sequence; oncogenes; oncogenic virus; plasma cell neoplasm; spleen; surface antigens; viral carcinogenesis

It is the long range purpose of this project to study the control mechanisms important in regulating cell growth, neoplastic transformation, and protein synthesis in normal and malignant cells of the immune system. To this end we are studying the structure of the proto-oncogenes in normal and tumor tissues from mouse and man and the expression of these oncogenes as mRNAs and proteins in mouse plasmacytomas and mouse and human myeloid and lymphoid tumors. In addition, we are investigating what role Abelson and Moloney leukemia viruses as well as recombinant viral constructs play in the induction of mouse tumors and alteration of their cellular oncogenes. We have discovered that Moloney leukemia viruses frequently insert themselves as proviruses in either the 5' end or 3' end of the mouse c-myb locus in certain myeloid tumors. We have isolated cDNA clones of murine and human c-myb transcripts from myeloid and lymphoid tumors and are characterizing these clones and the genes encoding c-myb in both these species. We have found that recombinant viruses containing mouse c-myc genes induce plasmacytomas or myeloid tumors in pristane-primed BALB/c mice; the nature of the viral oncogene determines the tumor type. Studies on these and other plasmacytomas indicate that expression of myc is regulated at a number of different metabolic sites. We have found that the very high levels of c-myc RNA in two of these tumors result from a combination of increased transcription of the c-myc gene and a stabilization of the c-myc RNA transcripts. We are studying whether these tumors with high c-myc RNA levels can constantly produce super abundant amounts of myc protein or if myc RNAs are subjected to translational control mechanisms. We are also studying how much translational controls operate in immunoglobulin synthesis in B lymphocytes.

研究控制是本项目的长远目标 调节细胞生长、肿瘤转化的重要机制， 以及免疫系统正常和恶性细胞中的蛋白质合成。 为此，我们正在研究正常人中原癌基因的结构。 小鼠和人的肿瘤组织以及这些癌基因的表达 作为小鼠浆细胞瘤以及小鼠和人类骨髓中的 mRNA 和蛋白质 和淋巴肿瘤。 此外，我们正在调查阿贝尔森扮演什么角色 和莫洛尼白血病病毒以及重组病毒构建体发挥作用 诱导小鼠肿瘤及其细胞的改变 癌基因。 我们发现莫洛尼白血病病毒经常 将自身作为原病毒插入小鼠的 5' 端或 3' 端 某些骨髓肿瘤中的 c-myb 位点。 我们已经分离出 cDNA 克隆 来自骨髓和淋巴肿瘤的小鼠和人类 c-myb 转录本 表征这些克隆以及编码 c-myb 的基因 物种。 我们发现含有小鼠c-myc的重组病毒 基因在降植烷引发的 BALB/c 中诱导浆细胞瘤或骨髓瘤 老鼠；病毒癌基因的性质决定了肿瘤类型。 研究 在这些和其他浆细胞瘤上表明 myc 的表达是 在许多不同的代谢位点受到调节。 我们发现 其中两个肿瘤中的 c-myc RNA 水平非常高，这是由于 c-myc 基因转录增加和 c-myc RNA 转录物的稳定性。 我们正在研究是否这些 c-myc RNA水平高的肿瘤可以不断产生超丰富的RNA myc 蛋白的量或 myc RNA 是否经过翻译 控制机制。 我们也在研究有多少翻译控制 参与 B 淋巴细胞的免疫球蛋白合成。