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激活 患病细胞和正常细胞中的特定基因 了解哪些基因可能在 恶性肿瘤、自身免疫性疾病和正常人的发展 差异化。 免疫系统被选为 这项研究的中心焦点，我们集中于 “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。 为此我们有 一直在研究淋巴肿瘤（特别是 BALB/cAnN 小鼠中定期诱导的浆细胞瘤 腹腔注射烷烃矿物油，例如降植烷。 这些肿瘤代表 B 淋巴细胞的永生系或 处于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了解基因如何 参与骨髓细胞和 B 细胞癌变的组织和 受监管。 一般来说，油诱导的浆细胞瘤仅在以下情况发生： 潜伏期长，一般为12个月。 在这么长的时间里 许多遗传变化可能已经积累的时期，一种或多种 其中更多可能与致癌有关 过程。 潜伏期可以大大缩短 注射某些逆转录病毒，例如阿贝尔森病毒复合体或 含有禽类 v-myc 基因的病毒。 潜伏期是 可能是通过提供一种基因损伤来缩短 偶然出现在经过油处理的腹膜细胞中。 我们还有 研究内源性原癌基因如何表达并发现 RNA稳态水平频繁升高 某些自身免疫性肿瘤中的原癌基因 c-myc 和 c-myb 细胞，以及分裂的正常淋巴细胞。 最近的研究有 显示了一些 ras 癌基因家族在大范围内的变化 这些肿瘤的数量。 这些细节和后果 目前正在分析突变。 另一个推定 癌基因 bcl-2 被发现仅在某些特定的情况下表达 B细胞分化期间。 广泛的努力已经 被用来表征表达的结构和控制 这些癌基因在正常和异常细胞中的分布。