INTERACTION OF ONCOGENES WITH AVIAN ERYTHROID CELLS

造血系统在动物的整个生命过程中发挥作用， 产生髓系、红系和淋巴系的成熟细胞。 这个系统是由细胞表面相互作用的复杂网络控制的 涉及细胞-细胞和细胞-生长因子系统。 白血病可以 被视为这些监管互动的崩溃。 我们的目标是 来确定这些控制生长的重要相互作用， 造血细胞的分化，以确定机制， 急性白血病能否提供一个独特的系统来研究 这一网络可能受到干扰。 鸟类逆转录病毒 是一种特别有吸引力模型系统， 他们提供了一个系统，造血细胞可以转化为 在体外，癌基因产物是膜糖蛋白，温度 敏感的突变体是可用的，其允许癌基因被 灭活 因此，有可能研究 病毒癌基因与细胞，并确定机制， 的细胞可以被扰动;此外， 癌基因的失活， 在控制随后的分化中起着重要作用 可以识别。 在这项建议中，我们的具体目标是： 1. 为了表征禽成红细胞增多症病毒S13的癌基因， 通过分子克隆原病毒并鉴定癌基因产物 负责细胞转化; 2. 利用现有的S13和禽成红细胞增多症的温度突变体， 病毒株ES 4，以研究这些癌基因的相互作用， 两种具有红系细胞的病毒;以及 3. 使用温度敏感的S13和AEV转化的成红细胞 与抗红细胞表面抗原的单克隆抗体一起， 识别在细胞凋亡中起作用的正常细胞表面受体， 红系细胞的分化，特别是鸡转铁蛋白 受体的

The hematopoietic system functions throughout the life of an animal to produce the mature cells of the myeloid, erythroid and lymphoid lineages. This system is controlled by a complex network of cell surface interactions involving both cell-cell and cell-growth factor systems. Leukemia can be viewed as a breakdown in these regulatory interactions. Our objectives are to identify these important interactions which control the growth and differentiation of hematopoietic cells in order to identify mechanisms that could acute leukemia provide a unique system to investigate possible mechanisms by which this network can be perturbed. The avian retroviruses that cause erythroblastosis are a particularly attractive model system in that they provide a system where hematopoietic cells can be transformed in vitro, the oncogene products are membrane glycoproteins, and temperature sensitive mutants are available which allow the oncogene to be inactivated. Therefore it is possible to study the interaction of the viral oncogene with the cell and to identify mechanisms by which the growth of of the cells can be perturbed; in addition, following thermal inactivation of the oncogene, normal cellular regulatory molecules which are playing important roles in controlling the subsequent differentiation can be identified. In this proposal our specific aims are: 1. to characterize, the oncogene of the avian erythroblastosis virus S13 by molecularly cloning the provirus and identifying the oncogene product responsible for cell transformation; 2. to use existing temperature mutants of S13 and avian erythroblastosis virus strain ES4 to investigate the interaction of the oncogenes of these two viruses with erythroid cells; and 3. to use the temperature sensitive S13 and AEV transformed erythroblasts together with monoclonal antibodies against erythroid surface antigens to identify normal cell surface receptors that play a role in the differentiation of erythroid cells, in particular the chicken transferrin receptor.