MALIGNANT BEHAVIOR AND CELLULAR ANTIGEN EXPRESSION

这个项目是关于染色体激活癌基因的。 易位。我们已经预测到小鼠浆细胞瘤(MPC)和 人类Burkitt淋巴瘤(BL)相关的染色体易位通过 将癌基因置于免疫球蛋白基因的直接控制下 轨迹。这一预测已被其他机构的分子研究所证实 实验室。由于易位，c-myc被并列到 IG-序列，并成为结构性激活。我们继续的工作是 重点关注由这些问题引起的细胞遗传学和分子问题 发现，特别是由基因突变引起的表型变化 易位及其在肿瘤发生过程中的作用。I.细胞遗传学 研究将集中在与小鼠浆细胞瘤(MPC)相关的 涉及c-myc区域的易位、倒位和缺失 Cr.15.我们还将探讨自发性大鼠免疫细胞瘤(RIC) 我们发现了导致重排的(6；7)易位 我的myc基因。在小鼠T细胞白血病中，我们将分析其作用 15-三体及其与c-myc和一些CHR的关系。15个本地化版本 病毒插入部位。II.与人类免疫缺陷相关的分子研究 细胞遗传学工作将集中在分析myc重排和 在“缺失”的浆细胞瘤中激活。我们将尝试克隆一个 发现两例可能由(12；14)易位激活的第二癌基因 MPC。我们从大鼠免疫细胞瘤中克隆了一个重排的c-myc基因，并 目前正在鉴定从CHR转座到它上面的序列。6.打开 小鼠T细胞淋巴瘤系统，我们正在研究可能的 CHRS上逆转录病毒插入位点之间的关系。15和17，以及 白血病相关的这些染色体的三体。体细胞杂种分析 在MPC和T细胞淋巴瘤系统中都被使用，以找到可能的 非法激活的基因表达之间的关系 MYC基因与正常人群融合后的致瘤行为 成纤维细胞。我们对c-myc基因表达调控的研究 转基因的正常和半白血病B细胞将探索两者之间的关系 在结构性激活的c-myc的表型效应和 蛋白质的数量。我们还将进行互补实验 探索myc蛋白能否替代某些腺病毒和EB病毒 函数。

This project deals with the activation of oncogenes by chromosomal translocations. We have predicted that the mouse plasmacytoma (MPC) and the human Burkitt lymphoma (BL) associated chromosome translocations act by bringing an oncogene under the direct control of an immunoglobulin gene locus. This prediction has been verified by molecular studies at other laboratories. Due to the translocation, the c-myc is juxtaposed to Ig-sequences and becomes constitutively activated. Our continued work is focused on cytogenetic and molecular problems that arise from these findings, particularly the phenotypic changes that result from the translocations and their role in the tumorigenic process. I. Cytogenetic studies will focus on the mouse plasmacytoma (MPC)-associated translocations, inversions and deletions that involve the c-myc region on chr. 15. We shall also explore the spontaneous rat immunocytomas (RIC) where we have found a (6;7) translocation that leads to the rearrangement of the myc gene. In mouse T-cell leukemia we shall analyze the role of 15-trisomy and its relationship to c-myc and a number of chr. 15 localized viral insertion sites. II. Molecular studies that relate to the cytogenetic work will focus on the analysis of the myc rearrangement and activation in the "deletion" plasmacytomas. We shall attempt to clone a possible second oncogene activated by a (12;14) translocation found in two MPCs. We have cloned a rearranged c-myc gene from a rat immunocytoma and are presently characterizing the sequence transposed to it from chr. 6. On the murine T-cell lymphoma system, we are studying the possible relationships between retroviral insertion sites on chrs. 15 and 17 and the leukemia associated trisomy of these chromosomes. Somatic hybrid analysis is used in both the MPC and the T cell lymphoma system, to find possible relationships between the expression of the illegitimately activated myc-gene and tumorigenic behavior, following fusion with normal fibroblasts. III. Our studies on the regulation of c-myc expression in transfected normal and semimalignant B-cells will explore the relationship between the phenotypic effects of constitutively activated c-myc and the quantity of the protein. We shall also perform complementation experiments to explore whether the myc protein can replace certain adeno- and EB-viral functions, respectively.