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; 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mRNA。 特别是我们专注于小鼠浆细胞瘤， 骨髓肿瘤和淋巴瘤，我们研究了什么作用 阿伯森和莫洛尼白血病病毒在诱导这种肿瘤中发挥了作用 以及细胞肿瘤的改变。 我们发现这些 病毒诱导形态上不同的肿瘤子集（ABPL） 由于插入了删除的莫洛尼的插入，改变了myb mRNA MYB基因中的白血病病毒。 这代表了一个哺乳动物的例子 通过启动子/增强子插入病毒的致癌基因激活。 ABPL 肿瘤现在似乎是髓生殖的，所以我们正在研究MYB 其他小鼠髓源性肿瘤中的基因。 c-myc的表达是 浆细胞瘤和染色体的某些浆细胞瘤增加 易位仅5'MYC EXON I，RNA转录利用了 两个MYC启动子的比率与正常细胞不同。 其中两个 浆细胞瘤是MYC RNA的超级生产商，正在研究 该增强RNA合成机制的线索。 我们也是 研究小鼠和人自身免疫性疾病中癌症的表达， 以及它们在小鼠和人类自身免疫中的癌基因的表达 疾病及其在正常淋巴细胞中的表达 有丝分裂剂。 某些类型的自身免疫性疾病的特征是高 MYC和RAF RNA的水平，而其他MYB RNA水平升高。