Linked Life Data

15379724

Source:http://linkedlifedata.com/resource/pubmed/id/15379724

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-9-21
pubmed:abstractText
Follicular thyroid carcinoma (FTC) accounts for approximately 20% of all thyroid cancers, and up to 40% of the deaths associated with this disease. Current treatment approaches include surgery, followed by radioactive iodine therapy. However, a significant proportion of locally advanced and metastatic FTC fails to concentrate iodine. Because traditional chemotherapeutic agents have not been shown to alter outcomes in this disease, novel therapeutic strategies are needed for advanced disease. Recently, a genomic rearrangement has been identified in up to 50% of FTC, involving a translocation event between chromosome regions 3p25 and 2q13. This translocation fuses the thyroid-specific transcription factor PAX8 gene with the PPARgamma gene, a ubiquitously expressed transcription factor. We have confirmed that this Pax8/PPARgamma fusion gene (designated PPFP) is an oncogene, which accelerates cell growth, reduces rates of apoptosis and permits anchorage independent and contact uninhibited growth of a thyroid cell line. The action of PPFP arises, at least in part, through its activity as a dominant-negative inhibitor of the wild-type PPARgamma transcription factor. Although the mechanism by which PPFP impairs PPARgamma activity remains unknown at this time, it is likely to be mediated by competition for the genomic PPARgamma response elements, the endogenous ligand, or various cofactors, including the Retinoid X Receptor (RXR). Consequently, modulation of PPFP activity might be possible through the use of PPARgamma agonists, RXR-agonists, or specific modulators of PPFP itself. Alternatively, modulation of several down-stream regulatory pathways may become possible, as the consequences of PPARgamma inhibition become better known. PPFP represents a potential novel target for the management of advanced FTC.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1568-0088
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
221-34
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
The PAX8/PPAR gamma fusion oncogene as a potential therapeutic target in follicular thyroid carcinoma.
pubmed:affiliation
Mayo Clinic & Foundation, Rochester, MN 55905, USA. mciver.bryan@mayo.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review, Research Support, Non-U.S. Gov't