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Constitutive β-catenin activation induces adrenal hyperplasia and promotes adrenal cancer development

2010; Oxford University Press; Volume: 19; Issue: 8 Linguagem: Inglês

10.1093/hmg/ddq029

1460-2083

Annabel Berthon, Isabelle Sahut‐Barnola, Sarah Lambert-Langlais, Cyrille de Joussineau, Christelle Damon‐Soubeyrand, Estelle Louiset, Mark M. Taketo, Frédérique Tissier, Jérôme Bertherat, Anne-Marie Lefrançois-Martinez, Antoine Martinez, Pierre Val,

Ovarian cancer diagnosis and treatment

Adrenocortical carcinoma is a rare but aggressive cancer with unknown aetiology. Constitutive activation of β-catenin is the most frequent alteration in benign and malignant adrenocortical tumours in patients. Here, we show that constitutive activation of β-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 β-catenin is an adrenal oncogene which triggers benign aldosterone-secreting tumour development and promotes malignancy.