Progression of BRAF-induced thyroid cancer is associated with epithelial-mesenchymal transition requiring concomitant MAP kinase and TGFΒ signaling Journal Article

   

Authors:	Knauf, J. A.; Sartor, M. A.; Medvedovic, M.; Lundsmith, E.; Ryder, M.; Salzano, M.; Nikiforov, Y. E.; Giordano, T. J.; Ghossein, R. A.; Fagin, J. A.
Article Title:	Progression of BRAF-induced thyroid cancer is associated with epithelial-mesenchymal transition requiring concomitant MAP kinase and TGFΒ signaling
Abstract:	Mice with thyroid-specific expression of oncogenic BRAF (Tg-Braf) develop papillary thyroid cancers (PTCs) that are locally invasive and have well-defined foci of poorly differentiated thyroid carcinoma (PDTC). To investigate the PTC-PDTC progression, we performed a microarray analysis using RNA from paired samples of PDTC and PTC collected from the same animals by laser capture microdissection. Analysis of eight paired samples revealed a profound deregulation of genes involved in cell adhesion and intracellular junctions, with changes consistent with an epithelial-mesenchymal transition (EMT). This was confirmed by immunohistochemistry, as vimentin expression was increased and E-cadherin lost in PDTC compared with adjacent PTC. Moreover, PDTC stained positively for phospho-Smad2, suggesting a role for transforming growth factor (TGF)Β in mediating this process. Accordingly, TGFΒ-induced EMT in primary cultures of thyroid cells from Tg-Braf mice, whereas wild-type thyroid cells retained their epithelial features. TGFΒ-induced Smad2 phosphorylation, transcriptional activity and induction of EMT required mitogen-activated protein kinase (MAPK) pathway activation in Tg-Braf thyrocytes. Hence, tumor initiation by oncogenic BRAF renders thyroid cells susceptible to TGFΒ-induced EMT, through a MAPK-dependent process. © 2011 Macmillan Publishers Limited All rights reserved.
Keywords:	thyroid; braf; epithelialmesenchymal transition; tgfΒ
Journal Title:	Oncogene
Volume:	30
Issue:	28
ISSN:	0950-9232
Publisher:	Nature Publishing Group
Date Published:	2011-07-14
Start Page:	3153
End Page:	3162
Language:	English
DOI:	10.1038/onc.2011.44
PROVIDER:	scopus
PMCID:	PMC3136543
PUBMED:	21383698
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-79960381628&partnerID=40&md5=563b4c55ac4132549f09dc865eb94f67
Notes:	--- - "Export Date: 17 August 2011" - "CODEN: ONCNE" - "Source: Scopus"

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