A Role for Bcl-2 in Notch1-Dependent Transcription in Thymic Lymphoma Cells.pdfVIP

Hindawi Publishing Corporation Advances in Hematology Volume 2012, Article ID 435241, 5 pages doi:10.1155/2012/435241 Research Article A Role for Bcl-2 in Notch1-Dependent Transcription in Thymic Lymphoma Cells Ronit Vogt Sionov, Shlomit Kfir-Erenfeld, Rachel Spokoini, and Eitan Yefenof The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel Correspondence should be addressed to Ronit Vogt Sionov, sionov@cc.huji.ac.il and Eitan Yefenof, eitany@ekmd.huji.ac.il Received 27 July 2011; Revised 19 October 2011; Accepted 21 October 2011 Academic Editor: Thomas G. Gross Copyright © 2012 Ronit Vogt Sionov et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notch1 is a transcription factor important for T-cell development. Notch1 is active in double negative (DN) thymocytes, while being depressed in double positive (DP) thymocytes. Synchronously, the expression of Bcl-2 becomes downregulated during the transition from DN to DP thymocytes. We previously observed that overexpression of an intracellular active Notch1 (ICN) in Bcl-2-positive 2B4 T cells leads to the transcription of Notch1-regulated genes. However, these genes were not induced in Bcl- 2-negative DP PD1.6 thymic lymphoma cells overexpressing ICN. Here we show that, when Bcl-2 is simultaneously introduced into these cells, Notch-regulated genes are transcribed. Only in the presence of both Bcl-2 and ICN, PD1.6 thymic lymphoma cells become resistant to glucocorticoid (GC)-induced apoptosis. Our data suggest that Bcl-2 plays a role in m