REGULATION OF APOPTOSIS IN NEUROBLASTOMA

点击翻译按钮获取中文摘要

This is application proposing to determine whether failure to undergo programmed cell death contributes to the pathogenesis of human neuroblastoma. Specifically, the investigator proposes to determine whether oncogene products which modulate programmed cell death (PCD) influence whether oncogene products which modulate programmed cell death (PCD) influence the malignant phenotype of neuroblastoma. The investigator previously determined that Bcl-2, which suppresses PCD, is present in pretreatment neuroblastoma tumore biopsies, and that, when deregulated, inhibits neuroblastoma tumor biopsies, and that, when deregulated, inhibits chemotherapy-induced PCD in neuroblastoma. Based on these prior findings, the investigator seeks to extend these observations in a system in which it is proposed that neuroblastoma is a disease resulting from failed apoptosis. The first aim will address the issue of oncogene cooperativity in the malignant phenotype of neuroblastoma,, specifically whether Bcl-2, in its capacity to inhibit apoptosis, cooperates with N-myc to transform cells. The second aim is proposed to determine whether Bcl-xs expression will lead to neuroblastoma cell death and enhanced response to chemotherapy (by pirating existing cell machinery). The third specific aim proposes to determine the expression of the death gene and survival gene in normal tissue from which neuroblastoma is thought to arise. The investigator feels these experiments will address the molecular link between the benign lesions and malignant neuroblastoma.