Constitutive β-catenin activation induces adrenal hyperplasia and promotes adrenal cancer development
Constitutive β-catenin activation induces adrenal hyperplasia and promotes adrenal cancer development
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DOI：
10.1093/hmg/ddq029
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发表时间：
2010-04-15
影响因子：
3.5
通讯作者：
Val, Pierre
中科院分区：
文献类型：
--
作者：
Berthon, Annabel;Sahut-Barnola, Isabelle;Val, Pierre
肾上腺皮质癌是一种罕见但侵袭性的癌症，病因不明。β-连环蛋白的组成性激活是良性和恶性肾上腺皮质肿瘤患者中最常见的改变。在这里，我们表明，β-连环蛋白在转基因小鼠肾上腺皮质的组成性激活导致进行性类固醇和未分化的梭形细胞增生以及发育不良的皮质和髓质。在17个月的时间过程中，转基因肾上腺发展恶性特征，如不受控制的新生血管和局部区域转移性浸润。这些致癌事件伴随着以束状细胞为代价的肾小球异位分化，这引起原发性醛固酮增多症。总之，这些观察结果表明，组成型活性β-连环蛋白是一种肾上腺癌基因，它触发良性醛固酮分泌肿瘤的发展，并促进恶性肿瘤。
Adrenocortical carcinoma is a rare but aggressive cancer with unknown aetiology. Constitutive activation of beta-catenin is the most frequent alteration in benign and malignant adrenocortical tumours in patients. Here, we show that constitutive activation of beta-catenin in the adrenal cortex of transgenic mice resulted in progressive steroidogenic and undifferentiated spindle-shaped cells hyperplasia as well as dysplasia of the cortex and medulla. Over a 17 months time course, transgenic adrenals developed malignant characteristics such as uncontrolled neovascularization and loco-regional metastatic invasion. These oncogenic events were accompanied by ectopic differentiation of glomerulosa at the expense of fasciculata cells, which caused primary hyperaldosteronism. Altogether these observations demonstrate that constitutively active beta-catenin is an adrenal oncogene which triggers benign aldosterone-secreting tumour development and promotes malignancy.