NCI CLINICAL INVESTIGATOR AWARD PROGRAM

在胚胎发育过程中，中枢神经系统的神经元和胶质细胞 是从快速增殖的原始细胞分化而来的 神经上皮细胞。人们对其分子机制知之甚少 神经元和神经胶质细胞的分化和增殖，但对 逆转录病毒致癌基因最近提供了一种研究这些 机械装置。Pp60c-src，转化的正常细胞同源基因 Rous肉瘤病毒pp60v-src蛋白在 胚胎神经元开始分化。最近，我建立了 Pp60c-src是大脑皮层神经元分化的产物。 发育中的小鸡胚胎。然而，它在那里的确切功能作用 仍然是未知的。正常细胞src基因在人卵巢癌组织中的表达 将对雏鸡小脑发育进行研究，以帮助破译 该基因在神经细胞和可能的神经胶质细胞分化中的作用。第一, 富含神经元和神经胶质细胞的细胞培养物将从胚胎制备 鸡小脑及pp60c-src在这些细胞培养中的表达 将通过免疫细胞化学进行研究。这项研究将确定一个 Pp60c-src在年轻神经元中的亚细胞定位 确定pp60c-src在神经胶质细胞中的表达水平 正常细胞。Pp60c-src在控制增殖或 神经胶质细胞的分化是由非常 类似但突变的蛋白pp60v-src在感染的大鼠中诱导胶质瘤 携带劳斯肉瘤病毒。要研究pp60v-src在 胶质瘤，一组小鼠的单抗将被制备出来 Rous肉瘤病毒(RSV)诱导的大鼠脑胶质瘤。这些单抗 抗体将被用来探测胶质瘤特异性抗原的表达 在发育中的老鼠脑中。肿瘤特异性抗原在不同发育阶段的表达 正常的神经发育可能表明肿瘤转化为 RSV感染的神经胶质细胞涉及重要基因的表达 胎儿发育。

During embryogenesis the neurons and glia of the central nervous system arise by differentiation from rapidly proliferating primitive neuroepithelial cells. Very little is known about the molecular mechanisms of neuronal and glial differentiation and proliferation, but the study of retroviral oncogenes has recently provided a means of investigating these mechanisms. pp60c-src, the normal cellular homolog of the transforming protein pp60v-src of Rous sarcoma virus, is expressed at elevated levels in embryonic neurons at the onset of differentiation. Recently, I established that pp60c-src was the product of differentiating neurons in the cerebullum of the developing chick embryo. However, its precise functional role there is still unknown. The expression of the normal cellular src gene in the developing chick cerebellum will be studied in order to help decipher the role of this gene in neuronal and possibly glial differentiation. First, cell cultures enriched for neurons and glia will be prepared from embryonic chick cerebellum and the expression of pp60c-src in these cell cultures will be studied by immunocytochemistry. This study will identify a subcellular localization for pp60c-src in the young neuron and will also determine the level of pp60c-src expression in glial cells compared to normal cells. A role for pp60c-src in controlling the proliferation or differentiation of glial cells is suggested by the ability of the very similar but mutant protein, pp60v-src, to induce gliomas in rats infected with Rous sarcoma virus. To investigate the action of the pp60v-src in gliomas, a panel of mouse monoclonal antibodies will be prepared against Rous sarcoma virus (RSV)-induced gliomas in rats. These monoclonal antibodies will be used to probe the expression of glioma-specific antigens in the developing rat brain. Expression of tumor-specific antigens during normal neural development may suggest that neoplastic transformation of glial cells by RSV involves expression of genes that are important during fetal development.