Nucks1 synergizes with Trp53 to promote radiation lymphomagenesis in mice
| Autor: | Yue, Yangbo, Leung, Stanley G, Liu, Yueyong, Huang, Yurong, Grundt, Kirsten, Østvold, Anne-Carine, Jen, Kuang-Yu, Schild, David, Mao, Jian-Hua, Wiese, Claudia |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
Lymphoma Genotype animal diseases Oncology and Carcinogenesis Gene Dosage Loss of Heterozygosity NUCKS1 Haploinsufficiency Kidney Inbred C57BL Transgenic Antibodies Immunophenotyping Mice Rare Diseases Neoplasms Monoclonal thymic lymphoma Genetics Animals 2.1 Biological and endogenous factors Alleles Comparative Genomic Hybridization Nuclear Proteins Hematology Phosphoproteins V(D)J recombination Up-Regulation Liver Radiation-Induced double-strand break repair Female Tumor Suppressor Protein p53 ionizing radiation Spleen DNA Damage |
| Zdroj: | Yue, Y; Leung, SG; Liu, Y; Huang, Y; Grundt, K; Østvold, AC; et al.(2016). Nucks1 synergizes with Trp53 to promote radiation lymphomagenesis in mice. Oncotarget, 7(38), 61874-61889. doi: 10.18632/oncotarget.11297. UC Davis: Retrieved from: http://www.escholarship.org/uc/item/56q1t6fn Oncotarget, vol 7, iss 38 |
| DOI: | 10.18632/oncotarget.11297. |
| Popis: | NUCKS1 is a 27 kD vertebrate-specific protein, with a role in the DNA damage response. Here, we show that after 4 Gy total-body X-irradiation, Trp53+/- Nucks1+/- mice more rapidly developed tumors, particularly thymic lymphoma (TL), than Trp53+/- mice. TLs in both cohorts showed loss of heterozygosity (LOH) of the Trp53+ allele in essentially all cases. In contrast, LOH of the Nucks1+ allele was rare. Nucks1 expression correlated well with Nucks1 gene dosage in normal thymi, but was increased in the majority of TLs from Trp53+/- Nucks1+/- mice, suggesting that elevated Nucks1 message may be associated with progression towards malignancy in vivo. Trp53+/- Nucks1+/- mice frequently succumbed to CD4- CD8- TLs harboring translocations involving Igh but not Tcra/d, indicating TLs in Trp53+/- Nucks1+/- mice mostly originated prior to the double positive stage and at earlier lineage than TLs in Trp53+/- mice. Monoclonal rearrangements at Tcrb were more prevalent in TLs from Trp53+/- Nucks1+/- mice, as was infiltration of primary TL cells to distant organs (liver, kidney and spleen). We propose that, in the context of Trp53 deficiency, wild type levels of Nucks1 are required to suppress radiation-induced TL, likely through the role of the NUCKS1 protein in the DNA damage response. |
| Databáze: | OpenAIRE |
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