MALIGNANT BEHAVIOR AND CELLULAR ANTIGEN EXPRESSION

本项目研究染色体对癌基因的激活作用。 易位 我们预测小鼠浆细胞瘤（MPC）和 人伯基特淋巴瘤（BL）相关染色体易位通过以下方式起作用： 将致癌基因置于免疫球蛋白基因的直接控制下 基因座 这一预测已被其他分子研究所证实。 laboratories. 由于易位，c-myc与 Ig序列，并成为组成性激活。 我们继续的工作是 专注于细胞遗传学和分子问题， 研究结果，特别是表型变化，导致从 易位及其在肿瘤发生过程中的作用。 I.细胞遗传 研究将集中在小鼠浆细胞瘤（MPC）相关的 涉及c-myc区域的易位、倒位和缺失， Chr. 15. 我们还将探讨自发性大鼠免疫细胞瘤（RIC） 我们发现了一个（6; 7）易位， myc基因。 在小鼠T细胞白血病中，我们将分析 15-三体性及其与c-myc和一些chr. 病毒插入位点。 二.分子研究， 细胞遗传学工作将集中于myc重排的分析， 在"缺失型"浆细胞瘤中激活。 我们将尝试克隆一个 可能的第二个癌基因激活的（12; 14）易位发现在两个 MPCs. 我们从大鼠免疫细胞瘤中克隆了重排的c-myc基因， 目前正在表征从第6章转置到它的序列。 对 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 白血病相关的三体性这些染色体。 体细胞杂种分析 用于MPC和T细胞淋巴瘤系统，以寻找可能的 表达非法激活的 myc基因和肿瘤发生行为，融合后与正常 成纤维细胞 三.我们对c-myc表达调控的研究 转染的正常和半恶性B细胞将探讨 在组成性激活的c-myc的表型效应和 蛋白质的量。 我们还将进行互补实验 探索myc蛋白是否可以取代某些腺病毒和EB病毒， 功能，分别。

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.