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.

这项研究的总体目标是研究激活 患病和正常细胞中的特定基因是为了 了解哪些基因可能在 恶性肿瘤，自身免疫性疾病和正常的发展 分化。 免疫系统被选为 这项研究的主要重点，我们专注于 表达“ Oncogenes”，尤其是MYC，MYB和RAS，以及 免疫球蛋白和T细胞受体基因。 为此，我们有 一直在研究淋巴样肿瘤（尤其是 浆细胞瘤）由BALB/CANN MICE定期诱导 腹膜内注射烷烃矿物油，例如丙烷。 这些肿瘤代表B淋巴细胞的永生线或 分化的不同阶段的髓样细胞。 目前我们 正在使用这种模型的肿瘤系统来了解基因 涉及髓样和B细胞致癌作用，并组织 受监管。 通常仅在 长时间的长时间，通常为12个月。 这么长时间 时期许多遗传变化可能积累了一个或一个 更多的可能与致癌有关 过程。 潜在时期可以大大缩短 注射某些逆转录病毒，例如阿伯森病毒复合物或 结合禽类V-MYC基因的病毒。 潜伏期是 缩短大概是通过提供一种遗传病变之一 在油处理的腹膜细胞中偶然出现。 我们也有 研究了如何表达和发现内次原始基因 从 原始癌基因C-MYC和C-MYB在某些肿瘤中，自身免疫性 细胞，并在正常的淋巴细胞中。 最近的研究 显示了大型癌基因的某些RAS家族的变化 这些肿瘤的数量。 这些细节和后果 目前正在分析突变。 另一个假定 癌基因Bcl-2仅表达 B细胞分化期间的时期。 广泛的努力 被制作表征表达的结构和控制 在正常和异常细胞中的这些癌基因。