Expression profiling of thymic lymphomas from p53 mutant (R270H) mice with varying HIF levels

ABSTRACT: Expression profiling of thymic lymphomas derived from HIF1a+/+, p53R270H/R270H; HIF1a+/-, p53R270H/R270H; and HIF1aKI/+, p53R270H/R270H mice. HIF1a and HIF2a share a high degree of sequence homology, but recent work has shown that the two a subunits can have contrasting and tissue-specific effects on tumor growth. To directly compare the role of each HIFa subunit in spontaneous tumorigenesis, we bred a mouse model of expanded HIF2a expression and Hif1a+/- mice to homozygotes for the R270H mutation in p53. Heterozygosity for Hif1a significantly reduced the incidence of thymic lymphomas observed in this model. Moreover, reduced Hif1a levels correlated with decreased stabilization of activated Notch1 and expression of the Notch target genes, Dtx1 and Nrarp. Keywords: genetic modification, disease state analysis Thymic lymphoma tissue was preserved at the time mice were sacrificed. 4-5 samples from each of 3 genotypes (HIF1a+/-, p53R270H/R270H, HIF1aKI/+; p53R270H/R270H; and HIF1a+/+, p53R270H/R270H) were then used for microarray analysis to identify differences in gene expression that could account for changes in tumor onset and incidence.

ORGANISM(S): Mus musculus

SUBMITTER: M. Celeste Simon 

PROVIDER: E-GEOD-14336 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress