title: Mutationally activated BRAF(V600E) elicits papillary thyroid cancer in the adult mouse.
abstract: Mutated BRAF is detected in approximately 45% of papillary thyroid carcinomas (PTC). To model PTC, we bred mice with adult-onset, thyrocyte-specific expression of BRAF(V600E). One month following BRAF(V600E) expression, mice displayed increased thyroid size, widespread alterations in thyroid architecture, and dramatic hypothyroidism. Over 1 year, without any deliberate manipulation of tumor suppressor genes, all mice developed PTC displaying nuclear atypia and marker expression characteristic of the human disease. Pharmacologic inhibition of MEK1/2 led to decreased thyroid size, restoration of thyroid form and function, and inhibition of tumorigenesis. Mice with BRAF(V600E)-induced PTC will provide an excellent system to study thyroid tumor initiation and progression and the evaluation of inhibitors of oncogenic BRAF signaling.
authors.affiliation: UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California, USA.
authors.forename: Roch-Philippe
authors.initials: RP
authors.lastname: Charles
authors.forename: Gioia
authors.initials: G
authors.lastname: Iezza
authors.forename: Elena
authors.initials: E
authors.lastname: Amendola
authors.forename: David
authors.initials: D
authors.lastname: Dankort
authors.forename: Martin
authors.initials: M
authors.lastname: McMahon
mesh_terms: D000818:Animals; D002277:Carcinoma; D002291:Carcinoma, Papillary; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D051379:Mice; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf