ORGANIZATION AND CONTROL OF GENETIC MATERIAL IN PLASMACYTOMAS

本研究的总体目标是研究脑电活动的激活。 疾病和正常细胞中的特定基因，以便 了解哪些基因可能在发育中发挥重要作用 恶性肿瘤、自身免疫性疾病和正常分化。 免疫系统已被选为这一问题的中心焦点 研究，我们集中在表达 “癌基因”，特别是myc、myb、ras和bc1-2，以及 免疫球蛋白和T细胞受体基因。为此，我们一直在 研究淋巴样肿瘤(尤其是浆细胞瘤) 在BALB/CANN小鼠体内有规律地通过腹腔注射诱导 注射烷烃矿物油，如普里斯坦。这些肿瘤 代表永生化的B淋巴细胞或髓系细胞系 分化的不同阶段。目前我们正在使用这个 肿瘤模型系统以了解基因如何参与髓系 和B细胞的致癌作用是有组织和受调控的。这个 Myc癌基因的激活已被清楚地证明是 对于浆细胞肿瘤的诱导是必不可少的，但它很可能 其他基因也必须被激活才能完成肿瘤 转型。癌基因ras家族是一个可能的候选基因。 我们有证据表明，这些基因中的一个或多个突变 可见于浆细胞瘤和淋巴肉瘤。他们所扮演的角色 这些肿瘤的发生机制正在研究中。MYB基因 在大多数造血肿瘤中表达，在某些病毒中也有表达 诱导的髓系恶性肿瘤它是通过插入一种 编码区内的病毒。该基因的调控 表达式正在调查中，其中一个替代方案是 在正常的和非正常的 恶性细胞。推测的原癌基因bc1-2似乎 在特定分化阶段和细胞类型中表达- 具体的方式。过度表达bc1-2是否会导致肿瘤 正在使用逆转录病毒结构对小鼠进行测试。

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 diseases 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, ras and bc1-2, 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. The activation of the myc oncogene has been clearly shown to be essential to the induction of plasma cell tumors, but it is likely that other genes must also be activated to complete the neoplastic transformation. The ras family of oncogenes is a likely candidate and we have evidence that mutations in one or more of these genes can be found in plasmacytomas and lymphosarcomas. The role these play in generation of these tumors is being studied. The myb gene is expressed in most hematopoietic tumors, and in certain virus= induced myeloid malignancies it is activated by insertion of a virus within the coding region. The regulation of this gene's expression is being investigated, and one example of alternative splicing of an extra coding exon has been found in normal and malignant cells. The putative proto-oncogene, bc1-2, appears to be expressed in a differentiation stage-specific and cell type- specific manner. Whether excess bc1-2 expression is tumorigenic in mice is being tested using retro- viral constructs.