Effect of Bcl11b genotypes and {gamma}-radiation on the development of mouse thymic lymphomas
- Department of Molecular Genetics, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi 1-757, Chuo-ku, Niigata 951-8510 (Japan)
- Department of Oral Health Science, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi 1-757, Chuo-ku, Niigata 951-8510 (Japan)
Bcl11b is a haploinsufficient tumor suppressor gene and expressed in many tissues such as thymus, brain and skin. Irradiated Bcl11b{sup +/-} heterozygous mice mostly develop thymic lymphomas, but the preference of Bcl11b inactivation for thymic lymphomas remains to be addressed. We produced Bcl11b{sup +/-} heterozygous and Bcl11b wild-type mice of p53{sup +/-} background and compared their incidence of {gamma}-ray induced thymic lymphomas. Majority of the tumors in p53{sup +/-} mice were skin tumors, and only 5 (36%) of the 14 tumors were thymic lymphomas. In contrast, Bcl11b{sup +/-}p53{sup +/-} doubly heterozygous mice developed thymic lymphomas at the frequency of 27 (79%) of the 34 tumors developed (P = 0.008). This indicates the preference of Bcl11b impairment for thymic lymphoma development. We also analyzed loss of the wild-type alleles in the 27 lymphomas, a predicted consequence given by {gamma}-irradiation. However, the loss frequency was low, only six (22%) for Bcl11b and five (19%) for p53. The frequencies did not differ from those of spontaneously developed thymic lymphomas in the doubly heterozygous mice, though the latency of lymphoma development markedly differed between them. This suggests that the main contribution of irradiation at least in those mice is not for the tumor initiation by inducing allelic losses but probably for the promotion of thymic lymphoma development.
- OSTI ID:
- 21143827
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 373, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2008.06.013; PII: S0006-291X(08)01157-1; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
Similar Records
Expression profiling reveals transcriptional regulation by Fbxw7/mTOR pathway in radiation-induced mouse thymic lymphomas
Development of prelymphoma cells committed to thymic lymphomas during radiation-induced thymic lymphomagenesis in B10 mice