Publication Date:
2000-08-26
Description:
Chromosomal translocations that encode fusion oncoproteins have been observed consistently in leukemias/lymphomas and sarcomas but not in carcinomas, the most common human cancers. Here, we report that t(2;3)(q13;p25), a translocation identified in a subset of human thyroid follicular carcinomas, results in fusion of the DNA binding domains of the thyroid transcription factor PAX8 to domains A to F of the peroxisome proliferator-activated receptor (PPAR) gamma1. PAX8-PPARgamma1 mRNA and protein were detected in 5 of 8 thyroid follicular carcinomas but not in 20 follicular adenomas, 10 papillary carcinomas, or 10 multinodular hyperplasias. PAX8-PPARgamma1 inhibited thiazolidinedione-induced transactivation by PPARgamma1 in a dominant negative manner. The experiments demonstrate an oncogenic role for PPARgamma and suggest that PAX8-PPARgamma1 may be useful in the diagnosis and treatment of thyroid carcinoma.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kroll, T G -- Sarraf, P -- Pecciarini, L -- Chen, C J -- Mueller, E -- Spiegelman, B M -- Fletcher, J A -- CA75425/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2000 Aug 25;289(5483):1357-60.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. tkroll@rics.bwh.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10958784" target="_blank"〉PubMed〈/a〉
Keywords:
Adenocarcinoma, Follicular/*genetics/metabolism
;
Adenoma/genetics/metabolism
;
Adult
;
Aged
;
Carcinoma, Papillary/genetics/metabolism
;
Cell Line
;
Cell Nucleus/metabolism
;
Child
;
DNA-Binding Proteins/chemistry/genetics/pharmacology/*physiology
;
Humans
;
Middle Aged
;
*Nuclear Proteins
;
Oncogene Proteins, Fusion/chemistry/genetics/*physiology
;
Paired Box Transcription Factors
;
Receptors, Cytoplasmic and Nuclear/chemistry/genetics/*physiology
;
Response Elements
;
Thiazoles/pharmacology
;
*Thiazolidinediones
;
Thyroid Neoplasms/*genetics/metabolism
;
Trans-Activators/chemistry/genetics/pharmacology/*physiology
;
Transcription Factors/chemistry/genetics/pharmacology/*physiology
;
Transcription, Genetic
;
Transcriptional Activation
;
Translocation, Genetic
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
