title: Constitutive beta-catenin activation induces adrenal hyperplasia and promotes adrenal cancer development.
abstract: 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.
authors.affiliation: Clermont Université, Université Blaise Pascal, GReD, BP 10448, F-63000 Clermont-Ferrand, France.
authors.forename: Annabel
authors.initials: A
authors.lastname: Berthon
authors.forename: Isabelle
authors.initials: I
authors.lastname: Sahut-Barnola
authors.forename: Sarah
authors.initials: S
authors.lastname: Lambert-Langlais
authors.forename: Cyrille
authors.initials: C
authors.lastname: de Joussineau
authors.forename: Christelle
authors.initials: C
authors.lastname: Damon-Soubeyrand
authors.forename: Estelle
authors.initials: E
authors.lastname: Louiset
authors.forename: Mark M
authors.initials: MM
authors.lastname: Taketo
authors.forename: Frédérique
authors.initials: F
authors.lastname: Tissier
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bertherat
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Lefrançois-Martinez
authors.forename: Antoine
authors.initials: A
authors.lastname: Martinez
authors.forename: Pierre
authors.initials: P
authors.lastname: Val
mesh_terms: D000302:Adrenal Cortex / Q000378:metabolism / Q000473:pathology*; D000310:Adrenal Gland Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D006801:Humans; D006965:Hyperplasia; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051176:beta Catenin; D000450:Aldosterone