CANCER AND CHROMOGRANIN A

嗜铬素A(CGA)是一种高相对分子质量的蛋白质，在 基本上都是人类的内分泌组织。它是与 特定的荷尔蒙形成每个组织在其正常和 恶性状态。因为它是由内分泌过量分泌的 CGA是一种新出现的内分泌癌的血清标志物。 然而，人们对CGA的监管知之甚少。 合成和分泌，因此没有挑衅性关于 CGA合成和排泄的调节，从而调节NO 已经开发出了对它的挑衅性测试。我们建议研究 CGA的生物合成和分泌及其与CGA的比较 它的相关激素之一，降钙素(CT)，在细胞中 产生这两种物质。这将在细胞系中完成 在我们的实验室建立，代表了三个 内分泌癌的类型。一种细胞系是从甲状腺衍生出来的 C细胞(甲状腺髓样癌)，从而产生CgA和 CT是真正意义上的。其他细胞系来自肺癌。 从而异位产生CGA和CT，其中一个来自经典的 还有一例来自一种变异型小细胞肺癌。我们会 CGA分泌的调节和协同调节的研究 和CT通过这些细胞的培养。有待研究的分泌物 包括矿物质、神经内分泌介体和多肽 荷尔蒙。“第二信使”的角色将由 测试福司可林、佛波醇酯和离子载体的效果。 CgA和CT的分泌将通过放射免疫测定进行评估 这两种物质已经在我们的 实验室。生物合成和转录的调控 对CGA的影响也将进行研究。这将通过脉冲来完成- Chase标记实验和通过使用的cdna探针 我们实验室开发的用于对CGA特异性mRNAs进行定量的。 因此，这些探头将被应用于对 应用重组DNA程序进行CGA的分子生物学研究。 这些关于CGA调节的信息将有助于我们的临床 目标是开发CGA的挑衅性测试，从而提炼 血清CgA检测在肿瘤诊断中的应用 标记物在慢性阻塞性肺疾病诊断和治疗中的应用 大量的内分泌肿瘤。RIA将应用于 对大量内分泌肿瘤患者的研究， 包括神经内分泌性肺癌，CGA是一种 潜在的血清标志物。这些基础和临床研究应该 帮助我们阐明其基础和临床意义。 CGA在内分泌癌中的作用

Chromogramin A (CgA) is a high MW protein that is found in essentially all human endocrine tissue. It is co-secreted with the specific hormone form each tissue in both its normal and malignant state. Because it is secreted in excess by endocrine tumors, CgA is an emerging serum marker for endocrine cancers. However, very little is known about the regulation of CgA synthesis and secretion and consequently no provocative about the regulation of CgA synthesis an descretion and consequently no provocative tests for it have been developed. We propose to study the biosynthesis and secretion of CgA and compare it to that of one of its associated hormones, calitonin (CT), in cells that produce both substances. This will be accomplished in cell lines established in our laboratory that are representative of three types of endocrine cancer. One cell line is derived form thyroidal C-cells (medullary thyroid carcinoma) and thus produces CgA and CT eutopically. The other cell lines are derived from lung tumors and thus produce CgA and CT ectopically, one from a classical and one from a variant small cell carcinoma of the lung. We shall study the regulation and the co-regulation of the secretion of CgA and CT by these cells in culture. The secretagogues to be studied include minerals, neuroendocrine mediators, and peptide hormones. The role of "second messengers" will be evaluated by testing the effects of forskolin, phorbol esters, and ionophores. Secretion of CgA and CT will be evaluated by radiommunoassays for the two substances which have been developed in our laboratories. The regulation of the bio-synthesis and transcription of CgA will also be studied. This will be accomplished by pulse- chase labeling experiments and through the use of cDNA probes developed in our laboratory to quantitate CgA-specific mRNAs. These probes will thus be applied to regulatory studies of the molecular biology of CgA using recombinant DNA procedures. This information about CgA regulation will facilitate our clinical goal which is to develop provocative tests for CgA and thus refine the use of the measurement of serum levels of CgA as a tumor marker in the diagnosis and management of patients with the large number of endocrine tumors. The RIA will be applied to studies of patients with the large number of endocrine tumors, including neuroendocrine lung cancer, for which CgA is a potential serum marker. These basic and clinical studies should help us to elucidate the fundamental and clinical significance of CgA in endocrine cancer.