Molecular Genetics Of Adrenocortical Tumors

这项工作的目标是了解导致影响肾上腺皮质的疾病的遗传和分子机制，重点是那些发育，遗传和与肾上腺发育不全或增生，多发性肿瘤和其他内分泌腺（特别是脑垂体和甲状腺）异常有关的疾病。我们研究了先天性肾上腺发育不全引起的三A综合征和多种内分泌缺陷，家族性醛固酮增多症，肾上腺皮质和甲状腺癌，垂体肿瘤和多发性内分泌瘤（MEN）综合征影响垂体，甲状腺和肾上腺，和卡尼综合征（CNC），一种常染色体显性遗传病。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、黑色素斑和痣）。我们已经确定了蛋白激酶A（PKA）的1-A型调节亚基，该亚基由PRKAR 1A基因编码，是大多数CNC患者的基因。因此，我们工作的一个重要部分现在集中在PKA刺激的信号通路，PKA对肿瘤抑制和/或发展的影响，细胞周期和染色体稳定性。这些项目由Prkar 1a特异性动物模型促进。

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-A 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.