Mutationally Activated BRAFV600E Elicits Papillary Thyroid Cancer in the Adult Mouse

被引：80

作者：

Charles, Roch-Philippe ^{[1
,2
]}

Iezza, Gioia ^{[3
]}

Amendola, Elena ^{[4
]}

Dankort, David ^{[1
,2
]}

McMahon, Martin ^{[1
,2
]}

机构：

[1] Univ Calif San Francisco, UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA

[2] Univ Calif San Francisco, Dept Cell & Mol Pharmacol, San Francisco, CA 94158 USA

[3] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94158 USA

[4] Biogem SC Ar l, Ist Ric Genet, Gaetano Salvatore, Ariano Irpino, Italy

来源：

CANCER RESEARCH | 2011年 / 71卷 / 11期

关键词：

TUMOR INITIATION; EXPRESSION; BRAF; PROGRESSION; MODELS; CELLS; GENE;

D O I：

10.1158/0008-5472.CAN-10-4463

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. Cancer Res; 71(11); 3863-71. (C) 2011 AACR.

引用

页码：3863 / 3871

页数：9

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