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Cancer Res. 2011 Jun 1;71(11):3863-71. doi: 10.1158/0008-5472.CAN-10-4463. Epub 2011 Apr 21.

Mutationally activated BRAF(V600E) elicits papillary thyroid cancer in the adult mouse.

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  • 1UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California, USA.

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.

PMID:
21512141
[PubMed - indexed for MEDLINE]
PMCID:
PMC3107361
Free PMC Article

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