The PAX8/PPAR gamma fusion oncogene as a potential therapeutic target in follicular thyroid carcinoma

Current Drug Targets. Immune, Endocrine and Metabolic Disorders
Bryan McIverNorman L Eberhardt

Abstract

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 rema...Continue Reading

Citations

Apr 20, 2011·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Lei CuiDayong Jin
Apr 25, 2012·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Wang XuqingZhang Jianxin
Nov 14, 2012·Therapeutic Advances in Endocrinology and Metabolism·David A Liebner, Manisha H Shah
Jun 30, 2006·Endocrine Journal·Jen-Der Lin, Tzu-Chieh Chao
Jul 22, 2014·Otolaryngologic Clinics of North America·Linwah Yip, Robert L Ferris
Mar 2, 2016·Nature Reviews. Clinical Oncology·Keith C Bible, Mabel Ryder
Nov 18, 2008·Hematology/oncology Clinics of North America·Ranee Mehra, Roger B Cohen
Aug 23, 2008·Biochimica Et Biophysica Acta·Mridula NambiarSathees C Raghavan
Mar 19, 2008·Current Problems in Surgery·Elizabeth G GrubbsDouglas B Evans
Aug 4, 2007·Endocrinology and Metabolism Clinics of North America·Catherine Dinauer, Gary L Francis
Aug 26, 2006·Nature Clinical Practice. Endocrinology & Metabolism·Massimo Santoro, Francesca Carlomagno
Oct 3, 2006·Trends in Molecular Medicine·Chandan Kumar-SinhaArul M Chinnaiyan
Aug 27, 2014·Journal of Surgical Oncology·Linwah Yip
Jul 30, 2015·Endocrine-related Cancer·Denise ZwanzigerDagmar Fuehrer
Sep 25, 2007·Arquivos brasileiros de endocrinologia e metabologia·Massimo Santoro, Alfredo Fusco
Jan 7, 2006·Nature Reviews. Cancer·Ewan J D RobsonMichael R Eccles
Aug 4, 2012·Molecular Medicine Reports·Giulia Costanza LeonardiMassimo Libra

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis