CHROMOGRANINS IN NEUROENDOCRINE TUMOR CELLS

颗粒蛋白是一个免疫学上不同的分泌蛋白家族 只在内分泌和神经细胞中表达， 它们的分泌产物储存在颗粒中， 刺激.在这些细胞中，颗粒蛋白是形成 在包装前在高尔基体中形成的致密核心基质， 分泌产物颗粒蛋白还具有许多蛋白水解作用， 来自颗粒蛋白前体的加工位点和肽已经被 显示具有重要的自分泌调节活性。 格兰宁是 内分泌肿瘤及其免疫细胞化学 在肿瘤组织中的检测被认为是诊断存在 神经内分泌组织。尽管有这些和其他关于颗粒蛋白的研究 结构和功能，组织特异性表达的分子基础 还有待研究。 本研究旨在 详细研究颗粒蛋白的单个成员的表达， 家族，分泌颗粒蛋白II（SgII），在大鼠垂体前叶和 以大鼠PC12和GH4C1神经内分泌细胞系为模型， SgII表达的分子基础。这些研究的结果 将确定SgII在神经内分泌系统中表达的位置、时间和方式。 细胞 这些研究将回答以下具体问题： 1.垂体前叶的哪些细胞表达SgII？ 2. SgII是否是垂体早期分化或肉芽化的标志物 发育中的脑下垂体 3. SgII启动子中的哪些顺式作用元件介导组织特异性 SgII在神经内分泌细胞中的表达，并能特异性反式作用于 确定介导神经内分泌特异性表达的因子？ 4.哪些顺式作用元件介导SgII的负调控 在PC12细胞中通过环AMP表达，并可特异性反式作用于 确定哪些因素介导了这一规定？ 这些研究的结果将提供第一个分析， SgII在神经内分泌细胞中表达的分子机制。

The granins are a family of immunologically distinct, secretory proteins that are expressed only in endocrine and neuronal cells that concentrate their secretory products in storage granules and release it upon stimulation. In these cells the granins are integral to the formation of the dense-core matrix which forms in the Golgi prior to packaging of the secretory products. The granins also possess a number of proteolytic processing sites and peptides derived from granin precursors have been shown to have important autocrine regulatory activity. The granins are secreted at high rates by endocrine neoplasms and their immunocytochemical detection in tumoral tissue is considered diagnostic of the presence of tissue of neuroendocrine origin. Despite these and other studies on granin structure and function, the molecular basis for tissue-specific expression of the granins has yet to be studied. The present study is designed to investigate in detail the expression of a single member of the granin family, secretogranin II (SgII), in the rat anterior pituitary gland and to use the rat PC12 and GH4C1 neuroendocrine cell lines as models to study the molecular basis of SgII expression. These results of these studies will establish where, when and how SgII is expressed in neuroendocrine cells. The following specific questions will be answered by these studies: 1. Which cells in the anterior pituitary gland express SgII? 2. Is SgII a marker for early pituitary differentiation or granulation in the developing pituitary gland? 3. Which cis-acting elements in the SgII promoter mediate tissue-specific expression of SgII in neuroendocrine cells and can specific trans-acting factors be identified which mediate neuroendocrine-specific expression? 4. Which cis-acting elements mediate negative regulation of SgII expression by cyclic AMP in PC12 cells and can specific trans-acting factors be identified which mediate this regulation? The results of these studies will provide the first analysis of the molecular mechanism for expression of SgII in neuroendocrine cells.