Research Paper Volume 1, Issue 1 pp 122—130
Moderate expression of TRF2 in the hematopoietic system increases development of large cell blastic T-cell lymphomas
- 1 The Salk Institute for Biological Studies, La Jolla, CA 92037
- 2 Current address: Biotype AG, Moritzburger Weg 67, 01109 Dresden, Germany
- 3 Department of Biomedical Sciences / INBB, University of Sassari Medical School, Viale San Pietro 43/C, 07100 Sassari (SS), Italy
Received: December 15, 2008 Accepted: January 20, 2009 Published: January 21, 2009
https://doi.org/10.18632/aging.100015How to Cite
Abstract
The telomeric repeat binding factor 2 (TRF2) plays a central role in the protection of chromosome ends by inhibiting telomeres from initiating a DNA damage cascade. TRF2 overexpression has been suggested to induce tumor development in the mouse, and TRF2 levels have been found increased in human tumors. Here we tested whether moderate expression of TRF2 in the hematopoietic system leads to cancer development in the mouse. TRF2 and a GFP-TRF2 fusion protein were introduced into hematopoietic precursors, and tested for function. TRF2 overexpressing cells were integrated into the hematopoietic system of C57BL/6J recipient mice, and animals were put on tumor watch. An increase in the development of T-cell lymphomas was observed in secondary recipient animals, however, overexpression of the TRF2 transgene was not detectable anymore in the tumors. The tumors were characterized as large cell blastic T-cell lymphomas and displayed signs of genome instability as evidenced by chromosome fusions. However, the rate of lymphoma development in TRF2-overexpressing animals was low, suggesting the TRF2 does not serve as a dominant oncogene in the system used.