PDGF RECEPTOR EXPRESSION IN GLIAL CELLS

胶质瘤是最常见和最恶性的原发脑肿瘤。 在成年人身上。目前的治疗方法包括随后的手术切除 通过化疗。然而，这些程序本身可能 转化病变周围的细胞，导致继发性 肿瘤。这项研究计划的长期目标是寻求 确定参与神经胶质细胞转化的机制。这些 研究将为胶质瘤的发展提供关键的见解 并可能确定用于治疗干预的新靶点。这个 提案的重点是这些机制的特征 负责胶质细胞中PDGFR的适当表达 辨析和检验这些机制是否 神经胶质瘤细胞有缺陷。它们的生理功能 PDGFR用于控制神经胶质细胞的生长和分化 发展。PDGFR在两组早期均可检测到过表达 以及晚期神经胶质瘤。初步数据表明，PDGFR 在胶质瘤细胞中转录产物对cAMP调节没有反应 就像在正常的神经胶质细胞中一样。假设是一种改变了的 PDGFR基因表达对cAMP调节的反应可能是其基础 肿瘤细胞的不受控制的增殖。具体目标 这一建议的目的是识别基因中的核苷酸序列 PDGFR基因和基因产物ghat参与cAMP- 依赖的监管机制，并为 这些因素在脑胶质瘤中诱导PDGFR异常表达 细胞。

Gliomas are the most common and malignant of primary brain tumors in adults. Current treatments include surgical removal followed by chemotherapy. However,these procedures may themselves transform cells surrounding the lesion, leading to secondary tumors. The long-term goal of this research program seeks to identify mechanisms involved in transformation of glia. These studies will provide key insights into the development of gliomas and may identify novel targets for therapeutic intervention. The proposal focuses on the characterization of the mechanisms responsible for appropriate PDGFR expression during glial cell differentiation and examination of whether these mechanisms are defective in glial tumor cells. They physiological function of PDGFR is to control glial cell growth and differentiation during development. Overexpression of PDGFR is detected in both early and late stages of gliomas. Preliminary data suggest the PDGFR transcript does not respond to cAMP regulation in glioma cells as it does in normal glia. The hypothesis is that an altered response of PDGFR gene expression to cAMP regulation may underlie the uncontrolled proliferation of tumor cells. The specific aims of this proposal are to identify nucleotide sequences within the PDGFR gene and gene product ghat are involved in the cAMP- dependent regulatory mechanisms, and to establish a role for these factors in inducing aberrant PDGFR expression in glioma cells.