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: 4691872
• 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/4691872
• 关键词: Abelson leukemia virus; 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. In particular we are focusing on mouse plasmacytomas, myelogenous tumors and lymphosarcomas, and we investigating what role Abelson and Moloney leukemia viruses play in the induction of such tumors and the alteration of cellular ongogenes. We have discovered that these viruses induce a morphologically distinct subset of tumors (ABPLs) which have altered myb mRNAs owing to the insertion of a deleted form of Moloney leukemia virus in the myb gene. This represents a mammalian example of oncogene activation by promoter/enhancer insertion of virus. The ABPL tumors now appear to be of myelogenous origin, so we are studying the myb genes in other mouse myelogenous tumors. The expression of c-myc is increased in plasmacytomas, and in certain plasmacytomas with chromosomal translocations just 5' of the myc exon I, RNA transcription utilizes the two myc promoters in a different ratio than in normal cells. Two of these plasmacytomas are super producers of myc RNA and are being studied for clues to the mechanism of this enhanced RNA synthesis. We are also studying the expression of oncogens in mouse and human autoimmune diseases, as well as their expression of oncogenes in mouse and human autoimmune diseases, as well as their expression in normal lymphocytes activated by mitogens. Certain classes of autoimmune diseases are characterized by high levels of myc and raf RNA, while others have elevated levels of myb RNA.

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 mRNA。 我们特别关注小鼠浆细胞瘤， 骨髓瘤和淋巴肉瘤，我们研究什么作用 阿贝尔森和莫洛尼白血病病毒在诱发此类肿瘤中发挥作用 和细胞癌基因的改变。 我们发现这些 病毒诱导形态上不同的肿瘤子集（ABPL）， 由于插入缺失形式的莫洛尼而改变了 myb mRNA myb基因中的白血病病毒。 这代表了哺乳动物的例子 通过病毒启动子/增强子插入激活癌基因。 ABPL 肿瘤现在似乎是骨髓起源的，所以我们正在研究 myb 其他小鼠骨髓性肿瘤中的基因。 c-myc的表达量为 在浆细胞瘤以及某些伴有染色体的浆细胞瘤中增加 仅在 myc 外显子 I 的 5' 易位，RNA 转录利用 两个 myc 启动子的比例与正常细胞中不同。 其中两个 浆细胞瘤是 myc RNA 的超级生产者，目前正在研究 揭示这种增强 RNA 合成的机制的线索。 我们也是 研究小鼠和人类自身免疫性疾病中致癌基因的表达， 以及它们在小鼠和人类自身免疫中的癌基因表达 疾病及其在正常淋巴细胞中的表达 有丝分裂原。 某些类别的自身免疫性疾病的特点是高 myc 和 raf RNA 水平升高，而其他人的 myb RNA 水平升高。