Journal Article

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

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 and Pierre Val

in Human Molecular Genetics

Volume 19, issue 8, pages 1561-1576
Published in print April 2010 | ISSN: 0964-6906
Published online January 2010 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddq029
Constitutive β-catenin activation induces adrenal hyperplasia and promotes adrenal cancer development

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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.

Journal Article.  9066 words.  Illustrated.

Subjects: Genetics and Genomics

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