New genes and/or molecular pathways associated with adrenal hyperplasias and related adrenocortical tumors.
New genes and/or molecular pathways associated with adrenal hyperplasias and related adrenocortical tumors.
复制标题
与肾上腺增生和相关肾上腺皮质肿瘤相关的新基因和/或分子途径。
DOI：
10.1016/j.mce.2008.11.010
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发表时间：
2009
影响因子：
4.1
通讯作者：
Stratakis,ConstantineA
中科院分区：
文献类型：
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作者：
Stratakis,ConstantineA
在过去10年中，我们研究了导致影响肾上腺皮质的疾病的遗传和分子机制，重点是那些发育性、遗传性和与肾上腺发育不全或增生、多发性肿瘤和其他内分泌腺异常有关的疾病。在这项工作的基础上，我们提出了一个假设，肾上腺皮质肿瘤的形成和环AMP依赖的信号通路在这一过程中的重要性。蛋白激酶A（PKA）的调节亚基1-α（RIα）（PRKAR 1A基因）在大多数Carney综合征和原发性色素性结节性肾上腺皮质病（PPNAD）患者中发生突变。磷酸二酯酶-11 A（PDE 11 A基因）和-8 B（PDE 8 B基因）突变在孤立性肾上腺增生和库欣综合征患者以及PPNAD患者中发现。PKA对肿瘤抑制和/或发展以及细胞周期的作用正变得越来越清楚：PKA和/或cAMP在肾上腺皮质中充当生长和增殖的协调者。相应基因被敲除的小鼠模型支持这一观点。目前正在全基因组范围内寻找与肾上腺肿瘤和相关疾病有关的其他基因;线粒体氧化途径参与肾上腺皮质肿瘤发生的最新证据来自于我们对罕见相关性的研究，例如易患肾上腺髓质肿瘤和相关肿瘤的疾病（Carney三联征，即副神经节瘤和胃间质肉瘤的二联体，或Carney-Stratakis综合征，遗传性平滑肌瘤病和肾癌综合征），这些疾病似乎与肾上腺皮质病变有关。
Over the course of the last 10 years, we have studied 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. On the basis of this work, we propose an hypothesis on how adrenocortical tumors form and the importance of the cyclic AMP-dependent signaling pathway in this process. The regulatory subunit type 1-α (RIα) of protein kinase A (PKA) (the PRKAR1A gene) is mutated in most patients with Carney complex and primary pigmented nodular adrenocortical disease (PPNAD). Phosphodiesterase-11A (the PDE11A gene) and -8B (the PDE8B gene) mutations were found in patients with isolated adrenal hyperplasia and Cushing syndrome, as well in patients with PPNAD. PKA effects on tumor suppression and/or development and the cell cycle are becoming clear: PKA and/or cAMP act as a coordinator of growth and proliferation in the adrenal cortex. Mouse models in which the respective genes have been knocked out see m to support this notion. Genome-wide searches for other genes responsible for adrenal tumors and related diseases are ongoing; recent evidece of the involvement of the mitochondrial oxidation pathway in adrenocortical tumorigenesis is derived from our study of rare associations such as those of disorders predisposing to adrenomedullary and related tumors (Carney triad, the dyad of paragangliomas and gastric stromal sarcomas or Carney–Stratakis syndrome, hereditary leiomyomatosis and renal cancer syndrome) which appear to be associated with adrenocortical lesions.