Differential effects of Vav-promoter-driven overexpression of BCLX and BFL1 on lymphocyte survival and B cell lymphomagenesis
Selma Tuzlak, Manuel D Haschka, Anna-Maria Mokina, Thomas Ruelicke, Suzanne Cory, Verena Labi, Andreas Villunger
FEBS JOURNAL | WILEY | Published : 2018
Overexpression of BCLX and BFL1/A1 has been reported in various human malignancies and is associated with poor prognosis and drug resistance, identifying these prosurvival BCL2 family members as putative drug targets. We have generated transgenic mice that express human BFL1 or human BCLX protein throughout the haematopoietic system under the control of the Vav gene promoter. Haematopoiesis is normal in both the Vav-BFL1 and Vav-BCLX transgenic (TG) mice and susceptibility to spontaneous haematopoietic malignancies is not increased. Lymphoid cells from Vav-BCLX TG mice exhibit increased resistance to apoptosis in vitro while most blood cell types form Vav-BFL1 TG mice were poorly protected. ..View full abstract
Awarded by Austrian Science Fund (FWF)
Awarded by MCBO Doctoral College 'Molecular Cell Biology and Oncology'
We thank all members of the Villunger laboratory for their support and advice. Special thanks to K. Rossi, C. Soratroi and I. Gaggl for animal care and excellent technical assistance, S. Herzog for reagents and L. Fava for helpful discussion. We also thank M. Herold (WEHI) for the anti-A1 antibody and J. Borst (NKI) for the anti-BFL1 antiserum. This work was supported by grants from the Austrian Science Fund (FWF), Grant I 3271 (FOR-2036), the MCBO Doctoral College 'Molecular Cell Biology and Oncology' (W1101) and the 'Osterreichische Krebshilfe Tirol'. MDH and ST are supported by a DOC-fellowship from the Austrian Academy of Science (OAW).