Molecular Genetics Of Adrenocortical Tumors

肾上腺皮质肿瘤的分子遗传学

• 批准号: 6813771
• 负责人: Constantine A. Stratakis
• 金额: --
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6813771
• 关键词: adrenal glands; adrenal hyperplasia; adrenal neoplasm; biological signal transduction; children; developmental disease /disorder; human subject; human tissue; hyperaldosteronism; molecular genetics; multiple endocrine neoplasia; neoplasm /cancer genetics; pituitary disorders; protein kinase A; thyroid disorder

The goal of this work is to understand the genetic and molecular mechanisms leading to disorders that affect the adrenal cortex, with emphasis on those that are developmental, hereditary and associated with adrenal hypoplasia or hyperplasia, multiple tumors and abnormalities in other endocrine glands (especially the pituitary gland and to a lesser extent the thyroid gland). We have studied congenital adrenal hypoplasia caused by triple A syndrome and multiple endocrine deficiencies, familial hyperaldosteronism, adrenocortical and thyroid cancer, pituitary tumors and multiple endocrine neoplasia (MEN) syndromes affecting the pituitary, thyroid and adrenal glands, and Carney complex (CNC), an autosomal dominant disease. CNC is a MEN syndrome affecting the pituitary, adrenal cortex, thyroid, and the gonads, and is associated with a variety of other tumors, including myxomas and schwannomas, and skin pigmentation defects (lentigines, cafe-au-lait spots, and nevi). We have identified the regulatory subunit type 1-? (RI???of protein kinase A (PKA), which is coded by the PRKAR1A gene as the gene responsible for most CNC patients. Thus, a significant part of our work is now focused on PKA-stimulated signaling pathways, PKA effects on tumor suppression and/or development, the cell cycle and chromosomal stability. These projects are facilitated by Prkar1a-specific animal models.

这项工作的目标是了解导致影响肾上腺皮质疾病的遗传和分子机制，重点关注那些发育性、遗传性以及与肾上腺发育不全或增生、多发性肿瘤和其他内分泌腺（尤其是内分泌腺）异常相关的疾病。垂体和较小程度的甲状腺）。我们研究了由 3A 综合征和多种内分泌缺陷引起的先天性肾上腺发育不全、家族性醛固酮增多症、肾上腺皮质癌和甲状腺癌、垂体肿瘤和影响垂体、甲状腺和肾上腺的多发性内分泌肿瘤 (MEN) 综合征以及卡尼复合体 (CNC)，一种常染色体显性遗传疾病。 CNC 是一种影响垂体、肾上腺皮质、甲状腺和性腺的 MEN 综合征，并与多种其他肿瘤相关，包括粘液瘤和神经鞘瘤以及皮肤色素沉着缺陷（雀斑、咖啡斑和痣） 。我们已经确定了调节亚基类型 1-? （蛋白激酶 A (PKA) 的 RI???，由 PRKAR1A 基因编码，是大多数 CNC 患者的基因。因此，我们工作的重要部分现在集中在 PKA 刺激的信号通路、PKA 对Prkar1a 特异性动物模型促进了肿瘤抑制和/或发展、细胞周期和染色体稳定性。