Separase Loss of Function Cooperates with the Loss of p53 in the Initiation and Progression of T- and B-Cell Lymphoma, Leukemia and Aneuploidy in Mice
Figure 6
Q-PCR analysis of lymphomas and carcinomas arising in the ESPL1+/hyp mice in varying p53 backgrounds reveals significant reduction of p53 and Separase mRNA levels.
Separase and p53 transcripts in various tumor tissues was compared across different mouse genotypes to matched wild type litter mate mouse tissue. (A) A comparison of the relative Separase mRNA expression levels in wild type and ESPL1 mutant mice in a C57BL/6 background indicates a significant reduction in Separase expression levels both in the ESPL1+/hyp, p53 −/− lymphoma tissue (P = 0.0003) as well as in the carcinomas from the ESPL1+/hyp, p53+/− mice (P = 0.007). (B) Relative mRNA expression levels of p53 in wild type and mutant mice in a C57BL/6 background are shown. Tissue taken from both tumor microenvironment and tumor tissue from the same ESPL1+/hyp, p53+/− mice show a significant reduction in p53 transcript levels compared to levels of p53 in wild type mice tissue (P = 0.003 and P = 0.004 respectively). RNA isolated from ESPL1+/hyp, p53 −/− mice lymphomas was used as a control for p53 transcript levels. (‘n’ denotes number of tumors and red star denotes significant difference compared to wild type tissue).