PMID- 16818623
OWN - NLM
STAT- MEDLINE
DCOM- 20060907
LR  - 20131121
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 66
IP  - 13
DP  - 2006 Jul 1
TI  - Conditional activation of RET/PTC3 and BRAFV600E in thyroid cells is associated 
      with gene expression profiles that predict a preferential role of BRAF in 
      extracellular matrix remodeling.
PG  - 6521-9
AB  - Papillary thyroid cancers (PTC) are associated with nonoverlapping mutations of 
      genes coding for mitogen-activated protein kinase signaling effectors (i.e., the 
      TK receptors RET or NTRK and the signaling proteins RAS and BRAF). We examined 
      the pattern of gene expression after activation of these oncoproteins in thyroid 
      PCCL3 cells, with the goal of identifying pathways or gene subsets that may 
      account for the phenotypic differences observed in human cancers. We hybridized 
      cDNA from cells treated with or without doxycycline to induce expression of 
      BRAF(V600E), RET/PTC3, or RET/PTC3 with small interfering RNA-mediated knockdown 
      of BRAF, respectively, to slides arrayed with a rat 70-mer oligonucleotide 
      library consisting of 27,342 oligos. Among the RET/PTC3-induced genes, 2,552 did 
      not require BRAF as they were similarly regulated by RET/PTC3 with or without 
      BRAF knockdown and not by expression of BRAF(V600E). Immune response and 
      IFN-related genes were highly represented in this group. About 24% of 
      RET/PTC3-regulated genes were BRAF dependent, as they were similarly modified by 
      RET/PTC3 and BRAF(V600E) but not in cells expressing RET/PTC3 with knockdown of 
      BRAF. A gene cluster coding for components of the mitochondrial electron 
      transport chain pathway was down-regulated in this group, potentially altering 
      regulation of cell viability. Metalloproteinases were also preferentially induced 
      by BRAF, particularly matrix metalloproteinase 3 (MMP3), MMP9, and MMP13. 
      Accordingly, conditional expression of BRAF was associated with markedly 
      increased invasion into Matrigel compared with cells expressing RET/PTC3. The 
      preferential induction of MMPs by BRAF could explain in part the more invasive 
      behavior of thyroid cancers with BRAF mutations.
FAU - Mesa, Cleo Jr
AU  - Mesa C Jr
AD  - Division of Endocrinology and Metabolism, University of Cincinnati College of 
      Medicine, 3125 Eden Avenue, Cincinnati, OH 45267, USA.
FAU - Mirza, Mana
AU  - Mirza M
FAU - Mitsutake, Norisato
AU  - Mitsutake N
FAU - Sartor, Maureen
AU  - Sartor M
FAU - Medvedovic, Mario
AU  - Medvedovic M
FAU - Tomlinson, Craig
AU  - Tomlinson C
FAU - Knauf, Jeffrey A
AU  - Knauf JA
FAU - Weber, Georg F
AU  - Weber GF
FAU - Fagin, James A
AU  - Fagin JA
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Isoenzymes)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-ret)
RN  - EC 2.7.10.1 (Ret protein, rat)
RN  - EC 2.7.11.1 (Braf protein, rat)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - N12000U13O (Doxycycline)
SB  - IM
MH  - Animals
MH  - Carcinoma, Papillary/genetics/metabolism/pathology
MH  - Cluster Analysis
MH  - Doxycycline/pharmacology
MH  - Extracellular Matrix
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic
MH  - Isoenzymes/biosynthesis/genetics
MH  - Matrix Metalloproteinases/biosynthesis/genetics
MH  - Proto-Oncogene Proteins B-raf/biosynthesis/*genetics
MH  - Proto-Oncogene Proteins c-ret/biosynthesis/*genetics
MH  - Rats
MH  - Thyroid Neoplasms/enzymology/*genetics/metabolism/pathology
EDAT- 2006/07/05 09:00
MHDA- 2006/09/08 09:00
CRDT- 2006/07/05 09:00
PHST- 2006/07/05 09:00 [pubmed]
PHST- 2006/09/08 09:00 [medline]
PHST- 2006/07/05 09:00 [entrez]
AID - 66/13/6521 [pii]
AID - 10.1158/0008-5472.CAN-06-0739 [doi]
PST - ppublish
SO  - Cancer Res. 2006 Jul 1;66(13):6521-9. doi: 10.1158/0008-5472.CAN-06-0739.