Gene expression changes resulting from attenuation of Dicer activity

ABSTRACT: Despite smaller primary tumor burdens, Pten-/-Dicer-/+ mice develop seminal vesicle obstruction at high penetrance by 32 weeks, which is in sharp contrast to that observed in Pten-/- mice. This phenomenon implies that tumors in Pten-/-Dicer-/+ mice are more locally invasive. To corroborate this invasive phenotype, we examined global changes in gene expression using Agilent 44k whole genome expression microarrays. A total of 544 genes were statistically significantly altered by at least 1.4 fold in either Pten-/-Dicer-/+ or Pten-/-Dicer-/- mice, or both mice, as compared with Pten-/- mice. Approximately 22% genes were altered in the same trend in both Pten-/-Dicer-/+ and Pten-/-Dicer-/- mice, while 70% genes were only significantly affected in Pten-/-Dicer-/- mice. Very few genes were differentially regulated between Pten-/-Dicer-/+ and Pten-/-Dicer-/- mice or were only altered in Pten-/-Dicer-/+ mice. Data analysis identified that a list of genes associated with epithelial-mesenchymal transition, cell adhesion, migration, and extracellular matrix deposition are statistically significantly altered in favor of tumor metastasis in the Pten-/-Dicer-/+ mice. QRT-PCR confirmed the changes in expression of some genes including growth factors (Tgfb1 and Ctgf), transcription factors (Snail, Twist2, and Foxc1), protease (MMPs etc.), and extracellular matrix components (Collagens). This finding corroborates the phenotypic invasiveness of the tumors in Pten-/-Dicer-/+ mice at a molecular level. Cancerous urogenital tissues from Pten-/- (Dicer WT), Pten-/-Dicer-/+ (Dicer HET), and Pten-/-Dicer-/- (Dicer KO) mice were profiled for gene expression, using Agilent microarrays. multiple group comparison

ORGANISM(S): Mus musculus

SUBMITTER: Chad Creighton 

PROVIDER: E-GEOD-42820 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress