SOMATOSTATIN RECEPTOR EXPRESSION IN PITUITARY TUMORS

这项建议的长期目标是推进我们的 对生长抑素基因表达在垂体中作用的认识 垂体肿瘤激素的发病机制及其调控 过度分泌。因为生长抑素是一种有效的抗增殖剂 在人类肿瘤中，生长抑素受体的基因介导其 据推测，其影响是肿瘤抑制基因。总体目标 这一建议的主要内容是：1)证明存在差异和 生长抑素受体亚型在垂体肿瘤中的特异性表达 在不同表型的人垂体瘤中；2)展示 生长抑素类似物奥曲肽的降压效果 垂体瘤患者生长激素分泌与肿瘤大小的关系 取决于并可以由特定的 生长抑素受体亚型基因；3)获得遗传学证据 生长抑素受体亚型基因作为肿瘤抑制因子的研究 人类脑下垂体瘤的基因，以及脑下垂体瘤表现出的 生长抑素受体亚型基因的等位基因丢失和/或突变。 一个突变型生长抑素受体亚型基因的鉴定 脑垂体瘤将是第一个突变的例子 抑制性G蛋白连锁受体，并可能提供一种新的 慢性阻塞性肺疾病治疗干预的药理学靶点 脑垂体瘤。

The long term objectives of this proposal are to advance our understanding of the role of somatostatin gene expression in pituitary pathogenesis and in the regulation of pituitary tumor hormone hypersecretion. Because somatostatin is a potent antiproliferative agent in human tumors, the genes for somatostatin receptors which mediate its effects are hypothesized to be tumor suppressor genes. The overall goals of this proposal are: 1) to demonstrate that there are differential and pituitary tumor-specific expression of somatostatin receptor subtypes among human pituitary tumors of different phenotypes; 2) to demonstrate that the efficacy of the somatostatin analogue Octreotide to decrease growth hormone secretion and tumor size in patients with pituitary tumors is dependent upon and can be predicted by the expression of specific somatostatin receptor subtype genes; and 3) to obtain genetic evidence that somatostatin receptor subtype genes function as tumor suppressor genes in human pituitary tumors, and that pituitary tumors exhibit allelic loss and/or mutations in somatostatin receptor subtype genes. Identification of a mutant somatostatin receptor subtype gene in pituitary tumors would be the first example of a mutation in an inhibitory G-protein-linked receptor, and may provide a new pharmacological target for therapeutic intervention for patients with pituitary tumors.