CHROMOGRANINS IN NEUROENDOCRINE TUMOR CELLS

颗粒蛋白是一种免疫上不同的分泌性蛋白家族。 仅在集中在内分泌和神经细胞中表达 他们的分泌产品储存在颗粒中，并在 刺激。在这些细胞中，颗粒素是形成 在包装之前在高尔基体内形成的致密核基质 分泌性产品。颗粒素还具有许多蛋白水解物。 来自格兰宁前体的加工位点和多肽 被证明具有重要的自分泌监管活动。这些颗粒剂是 内分泌肿瘤及其免疫细胞化学的高分泌 在肿瘤组织中的检测被认为是对存在 神经内分泌来源的组织。尽管有这些和其他关于格兰宁的研究 结构和功能--组织特异性表达的分子基础 其中的颗粒物还有待研究。这项研究的目的是 详细研究单个Granin成员的表达 分泌颗粒素II(SgII)家族在大鼠垂体前叶和 以大鼠神经内分泌细胞系PC12和GH4C1为模型进行研究 SgII表达的分子基础。这些研究的结果 将确定SgII在神经内分泌中的表达地点、时间和方式 细胞。 这些研究将回答以下具体问题： 1.垂体前叶哪些细胞表达SgII？ 2.SGII是否是早期垂体分化或肉芽形成的标志 发育中的脑垂体腺？ 3.SgII启动子中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及CaN特异性反式作用 影响神经内分泌特异性表达的因素是什么？ 4.哪些顺式作用元件介导SgII的负性调控 环磷酸腺苷在PC12细胞中的表达及CaN特异性反式作用 确定哪些因素调节了这一规定？ 这些研究的结果将提供对 神经内分泌细胞表达SgII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.