ORGANIZATION AND CONTROL OF GENETIC MATERIAL IN PLASMACYTOMAS

我们的研究目标是了解其结构或结构发生变化的基因 表达在恶性肿瘤、自身免疫性疾病和 正常分化。我们关注的是一群人的表达 在这些癌基因中：abl、bcl2、bcl3和myc，以及潜在的 小鼠造血中的癌基因Pvt-1、蛋白激酶C(PKC)和细胞周期蛋白 肿瘤。继发于染色体的myc基因的非调控表达 易位已被证明是遗传的一个重要组成部分。 与石油诱导的IP有关的变化。BALB/c小鼠的浆细胞瘤。 其中一些激活myc的易位发生在200-300kb的c-myc 3‘端。 一个叫做PVT-1的区域。我们已经证明了这个基因座是在 在正常细胞中含量很低，但在一些细胞中含量要高得多 浆细胞瘤和某些B淋巴细胞株中c-myc 扩增出pvt-1基因。正常脾淋巴细胞和NIH3T3细胞 在有丝分裂刺激后增加其PVT-1的表达， 这表明PVT-1是“早期反应”基因的一个新成员， 尽管它的功能仍不清楚。人类和老鼠的同源性有 被检测到，表明进化守恒，并暗示一种功能 这对正常的生长或发育是必不可少的。 表达v-abl和c-myc的ABL-myc逆转录病毒可迅速诱导 BALB/c和其他品系小鼠的腹膜内浆细胞瘤 抵抗Pristane诱导的浆细胞瘤形成。如果老鼠是 预免疫后，50%的人会患上产生特异性抗体的肿瘤 对抗免疫原。事实证明，这是一种有用的替代方案。 到杂交瘤技术，用于产生各种单抗 抗原性。 PKC家族的七种同工酶已被证明在一个细胞中表达。 造血细胞和细胞系中的特定类型时尚。这些丝氨酸- 苏氨酸激酶被证明可以改变NIH3T3细胞的表型 当被转染的表达载体过表达时，以及免疫荧光 对同型特异性抗体的研究表明，每种同型 其激酶活性后转位到不同的亚细胞位置 已被佛波酯激活。同样，过度表达某些 小鼠髓系细胞系中的PKcs使这些细胞具有 对佛波酯刺激的反应是分化成巨噬细胞。

Our research goal is to understand the genes whose altered structure or expression play critical roles in malignancy, autoimmune diseases and normal differentiation. We are concentrating on the expression of a group of these "oncogenes": abl, bcl-2, bcl-3 and myc, as well as the potential oncogenes, Pvt-1, Protein Kinases C (PKC) and cyclins, in mouse hemopoietic tumors. Deregulated expression on myc secondary to chromosome translocation has been shown to be one essential component of the genetic alterations involved in oil-induced i.p. plasmacytomas in BALB/c mice. Some of these myc-activating translocations occur 200-300 kb 3' of c-myc in a region called Pvt-1. We have shown that this locus is transcribed at very low levels in normal cells but in much higher amounts in some plasmacytomas and in certain B lymphocytic cell lines in which both c-myc and Pvt-1 genes are amplified. Normal splenic lymphocytes and NIH3T3 cells increase their expression of Pvt-1 following mitogenic stimulation, suggesting that Pvt-1 is a new member of the "early response" genes, although its function remains unknown. Human and mouse homologies have been detected, indicating evolutionary conservation and implying a function that is essential to normal growth or development. The ABL-MYC retrovirus, expressing v-abl and c-myc, rapidly induces intraperitoneal plasmacytomas in BALB/c and other strains of mice that are resistant to pristane-induced plasmacytomagenesis. If the mice are preimmunized, 50% develop tumors producing antibody specifically directed against the immunogen. This has already proved to be a useful alternative to hybridoma technology for generating monoclonal antibodies to a variety of antigens. Seven isozymes of the PKC family have been shown to be expressed in a cell- type specific fashion in hemopoietic cells and cell lines. These serine- threonine kinases have been shown to change the phenotype of NIH3T3 cells when overexpressed by transfected expression vectors, and immunofluorescent studies with isotype-specific antibodies indicate that each isotype translocate to different subcellular locations after its kinase activity has been activated by phorbol ester. Similarly, overexpression of certain PKCs in mouse myeloid cell lines imparts to these cells the ability to respond to phorbol ester stimulation by differentiating into macrophages.