Source:http://linkedlifedata.com/resource/pubmed/id/17363500
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2007-3-16
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| pubmed:abstractText |
B-Raf is an important mediator of cell proliferation and survival signals transduced via the Ras-Raf-MEK-ERK cascade. BRAF mutations have been detected in several tumors, including papillary thyroid carcinoma, but the precise role of B-Raf as a therapeutic target for thyroid carcinoma is still under investigation. We analyzed a panel of 93 specimens and 14 thyroid carcinoma cell lines for the presence of BRAF mutations and activation of the mitogen-activated protein/ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. We also compared the effect of a B-Raf small inhibitory RNA construct and the B-Raf kinase inhibitor AAL881 on both B-Raf wild-type and mutant thyroid carcinoma cell lines. We found a high prevalence of the T1799A (V600E) mutation in papillary and anaplastic carcinoma specimens and cell lines. There was no difference in patient age, B-Raf expression, Ki67 immunostaining, or clinical stage at presentation between wild-type and BRAF(V600E) specimens. Immunodetection of phosphorylated and total forms of MEK and ERK revealed no difference in their phosphorylation between wild-type and BRAF(V600E) patient specimens or cell lines. Furthermore, a small inhibitory RNA construct targeting the expression of both wild-type B-Raf and B-Raf(V600E) induced a comparable reduction of viability in both wild-type and BRAF(V600E) mutant cancer cells. Interestingly, AAL881 inhibited MEK and ERK phosphorylation and induced apoptosis preferentially in BRAF(V600E)-harboring cells than wild-type ones, possibly because of better inhibitory activity against B-Raf(V600E). We conclude that B-Raf is important for the pathophysiology of thyroid carcinomas irrespective of mutational status. Small molecule inhibitors that selectively target B-Raf(V600E) may provide clinical benefit for patients with thyroid cancer.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AAL 881,
http://linkedlifedata.com/resource/pubmed/chemical/BRAF protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/Isoquinolines,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins B-raf,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger
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| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
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| pubmed:issn |
1535-7163
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| pubmed:author |
pubmed-author:BattDavidD,
pubmed-author:FanourakisGalinosG,
pubmed-author:McMillinDouglas WDW,
pubmed-author:McMullanCiaranC,
pubmed-author:MitsiadesConstantine SCS,
pubmed-author:MitsiadesNicholasN,
pubmed-author:NegriJosephJ,
pubmed-author:PoulakiVassilikiV,
pubmed-author:SozopoulosEliasE,
pubmed-author:Tseleni-BalafoutaSophiaS,
pubmed-author:VoutsinasGerassimosG
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| pubmed:issnType |
Print
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| pubmed:volume |
6
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1070-8
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:17363500-Adenocarcinoma, Follicular,
pubmed-meshheading:17363500-Adult,
pubmed-meshheading:17363500-Aged,
pubmed-meshheading:17363500-Apoptosis,
pubmed-meshheading:17363500-Carcinoma,
pubmed-meshheading:17363500-Carcinoma, Papillary,
pubmed-meshheading:17363500-Carcinoma, Squamous Cell,
pubmed-meshheading:17363500-Cell Proliferation,
pubmed-meshheading:17363500-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:17363500-Female,
pubmed-meshheading:17363500-Humans,
pubmed-meshheading:17363500-Isoquinolines,
pubmed-meshheading:17363500-Male,
pubmed-meshheading:17363500-Middle Aged,
pubmed-meshheading:17363500-Mitogen-Activated Protein Kinases,
pubmed-meshheading:17363500-Mutation,
pubmed-meshheading:17363500-Phosphorylation,
pubmed-meshheading:17363500-Proto-Oncogene Proteins B-raf,
pubmed-meshheading:17363500-RNA, Messenger,
pubmed-meshheading:17363500-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:17363500-Signal Transduction,
pubmed-meshheading:17363500-Thyroid Neoplasms,
pubmed-meshheading:17363500-Tumor Cells, Cultured
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| pubmed:year |
2007
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| pubmed:articleTitle |
Targeting BRAFV600E in thyroid carcinoma: therapeutic implications.
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| pubmed:affiliation |
Department of Medical Oncology, Dana-Farber Cancer Institute, Mayer Building, Room M555, 44 Binney Street, Boston, MA 02115, USA. Constantine_Mitsiades@dfci.harvard.edu
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| pubmed:publicationType |
Journal Article
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