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.

研究控制是该项目的远距离目的 机制对于调节细胞生长，肿瘤转化，重要的机制 免疫系统正常和恶性细胞中的蛋白质合成。 为此，我们正在研究正常原始基因的结构 来自小鼠和人的肿瘤组织以及这些癌基因的表达 作为小鼠血浆中的mRNA和蛋白质，小鼠和人类髓样 和淋巴肿瘤。 此外，我们正在研究阿伯森的角色 和Moloney白血病病毒以及重组病毒构建体 在诱导小鼠肿瘤和细胞的改变中 癌基因。 我们发现莫洛尼白血病病毒经常 将自己插入鼠标的5端或3'末端 某些髓样肿瘤中的C-MYB基因座。 我们有孤立的cDNA克隆 来自髓样和淋巴样肿瘤的鼠和人C-MYB转录本，是 表征这些克隆和编码C-MYB的基因 物种。 我们发现含有小鼠C-myc的重组病毒 基因诱导pristane-pristane-prist的balb/c中的浆细胞瘤或髓样肿瘤 小鼠；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 在许多不同的代谢部位调节。 我们发现 在其中两个肿瘤中，非常高的C-myc RNA是由a产生的 C-MYC基因和A的转录增加的组合 C-MYC RNA转录物的稳定化。 我们正在研究这些是否 高C-MYC RNA水平的肿瘤会不断产生超级丰富 MYC蛋白的数量或MYC RNA经过翻译 控制机制。 我们还在研究多少转化控制 在B淋巴细胞中的免疫球蛋白合成中作战。