Skip Navigation


Carcinogenesis Advance Access originally published online on April 29, 2007
Carcinogenesis 2007 28(10):2069-2073; doi:10.1093/carcin/bgm107
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrowOA All Versions of this Article:
28/10/2069    most recent
bgm107v2
bgm107v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Pérez-Mancera, P. A.
Right arrow Articles by Sánchez-García, I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pérez-Mancera, P. A.
Right arrow Articles by Sánchez-García, I.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Fat-specific FUS-DDIT3-transgenic mice establish PPAR{gamma} inactivation is required to liposarcoma development

Pedro Antonio Pérez-Mancera{dagger}, Carolina Vicente-Dueñas{dagger}, Inés González-Herrero, Manuel Sánchez-Martín1, Teresa Flores-Corral2 and Isidro Sánchez-García*

Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas/Universidad de Salamanca, Campus Unamuno, 37007 Salamanca, Spain
1 Department of Medicine
2 Servicio de Anatomía Patológica, Universidad de Salamanca, Campus Unamuno, 37007 Salamanca, Spain

* To whom correspondence should be addressed. Tel: +34 923 238403; Fax: +34 923 294813; Email: isg{at}usal.es

FUS-DDIT3 is a chimeric oncogene generated by the most common chromosomal translocation t(12;16)(q13;p11) associated to liposarcomas. The application of transgenic methods and the use of primary mesenchymal progenitor cells to the study of this sarcoma-associated FUS-DDIT3 gene fusion have provided insights into their in vivo functions and suggested mechanisms by which lineage selection may be achieved. These studies indicate that FUS-DDIT3 contributes to differentiation arrest acting at a point in the adipocyte differentiation process after induction of peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) expression. To test this idea within a living mouse, we generated mice expressing FUS-DDIT3 within aP2-positive cells, because aP2 is a downstream target of PPAR{gamma} expressed at the immature adipocyte stage. Here, we report that FUS-DDIT3 expression was successfully induced at the aP2 stage of differentiation both in vivo and in vitro. aP2-FUS-DDIT3 mice do not develop liposarcomas and exhibit an increase in white adipose tissue size. Consistent with in vivo data, mouse embryonic fibroblasts (MEFs) obtained from aP2-FUS-DDIT3 mice not only were capable of terminal differentiation but also showed an increased capacity for adipogenesis in vitro compared with wild-type MEFs. Taken together, this study provides genetic evidence that the presence of FUS-DDIT3 in an aP2-positive cell is not enough to cause liposarcoma development and establishes that PPAR{gamma} inactivation is required for liposarcoma development.

Abbreviations: BAT, brown adipose tissue; MEF, mouse embryonic fibroblast; PBS, phosphate-buffered saline; PPAR{gamma}, peroxisome proliferator-activated receptor {gamma}; WAT, white adipose tissue

{dagger} These authors contributed equally to this work.

Received March 2, 2007; revised March 27, 2007; accepted April 24, 2007.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.