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: 3939323
• 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/3939323
• 关键词: Abelson leukemia virus; B lymphocyte; alkanes; cell growth regulation; cellular oncology; chemical carcinogenesis; cytogenetics; disease /disorder model; 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; molecular cloning; molecular oncology; mouse leukemia; myelofibrosis; neoplasm /cancer genetics; neoplasm /cancer immunology; nucleic acid sequence; oncogenes; plasma cell neoplasm; spleen; surface antigens; viral carcinogenesis

The overall goal of this research is to study the activation of particular genes in diseased and normal cells in order to understand which genes may play important roles in the development of malignancies, autoimmune disease and normal differentiation. The immune system has been chosen as the central focus of this research, and we have concentrated on the expression of "oncogenes," especially myc, myb and ras, as well as immunoglobulin and T cell receptor genes. To this end we have been studying the lymphoid tumors (particularly the plasmacytomas) that are regularly induced in BALB/cAnN mice by intraperitoneal injections of alkane mineral oils, such as pristane. These tumors represent immortalized lines of B lymphocytes or myeloid cells at different stages of differentiation. Currently we are using this model system of tumors to learn how the genes involved in myeloid and B cell carcinogenesis are organized and regulated. Generally oil-induced plasmacytomas arise only after a long latent period, typically 12 months. In such a long time period many genetic changes could have accumulated, one or more of which could be causally involved in the carcinogenic process. The latent period can be drastically shortened by injecting certain retroviruses, e.g., Abelson virus complex or viruses incorporating avian v-myc genes. The latency period is shortened presumably by supplying one of the genetic lesions that by chance arose in the oil-treated peritoneal cells. We have also studied how endogeneous proto-oncogenes are expressed and found the frequent elevation of steady state levels of RNA from the proto-oncogenes c-myc and c-myb in certain tumors, autoimmune cells, and in dividing normal lymphocytes. Recent studies have shown changes in some of the ras family of oncogenes in a large number of these tumors. The details and consequences of these mutations are currently being analyzed. Another putative oncogene, bcl-2, has been found to be expressed at only certain periods during B cell differentiation. An extensive effort has been made to characterize the structure and control of expression of these oncogenes in normal and abnormal cells.

本研究的总体目标是研究 患病和正常细胞中的特定基因， 了解哪些基因可能在这些疾病中发挥重要作用。 恶性肿瘤、自身免疫性疾病和正常 分化 免疫系统被选为 这项研究的中心焦点，我们集中在 癌基因的表达，尤其是myc、myb和ras，以及 免疫球蛋白和T细胞受体基因。 为此， 一直在研究淋巴肿瘤（特别是 浆细胞瘤），其在BALB/cAnN小鼠中由 腹膜内注射烷烃矿物油，如降植烷。 这些肿瘤代表了B淋巴细胞或 不同分化阶段的骨髓细胞。 目前我们 正在使用这个肿瘤模型系统来研究基因是如何 参与骨髓和B细胞癌变的细胞被组织起来， 监管. 通常，油诱导的浆细胞瘤仅在 潜伏期很长，一般为12个月。 很久 许多遗传变化可能已经积累，一个或 其中更多的可能与致癌物质有关， 过程 潜伏期可以大大缩短， 注射某些逆转录病毒，例如，艾贝尔逊病毒复合体或 整合了禽类v-myc基因的病毒。 潜伏期为 可能是因为提供了一种遗传损伤， 偶然出现在油处理的腹膜细胞中。 我们还 研究了内源性原癌基因是如何表达和发现的 从细胞中RNA稳态水平的频繁升高， 某些肿瘤中的原癌基因c-myc和c-myb，自身免疫 细胞，以及分裂的正常淋巴细胞。 最近的研究 显示在一个大的肿瘤细胞中，ras癌基因家族中的一些发生了变化。 这些肿瘤的数量。 这些事件的细节和后果 目前正在对突变进行分析。 另一个假定的 已经发现癌基因bcl-2仅在某些特定的细胞中表达， 在B细胞分化过程中。 一项广泛的努力 已经被用来描述表达的结构和控制 这些癌基因在正常和异常细胞中的表达。