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Series GSE96545 Query DataSets for GSE96545
Status Public on Mar 14, 2017
Title Transcriptome profiling of dorsal prostate from four mouse genotypes : wild-type, LXRalpha/beta KO, PTENpc-/- and LXRalpha/beta KO PTENpc-/-
Organism Mus musculus
Experiment type Expression profiling by array
Summary Advanced prostate cancer (PCa) is a clinical challenge as this state of the disease lacks of curative therapeutic. We exploited human datasets as well as mouse models to decipher mechanisms able to constrain cancer evolution in response to genetic alteration that occurs in PCa. Careful analysis of transcriptomic signature of various PCa datasets reveals activation of the LXR target gene signature. This LXR signature is tightly correlated to PTEN-loss in human. Causal LXR deregulation has been confirmed using prostate mouse carcinomas from Pten-null mutant. Protective role of LXR has been demonstrated by their deletions in a Pten-null context in mouse prostate, thus results in an increase of PCa invasiveness and metastatic dissemination. PTEN deletion governs LXR transcriptional activity through deregulation of cholesterol de novo synthesis that leads to the accumulation of LXR ligands. According to these observations, pharmacological inhibition of cholesterol biosynthesis using statins abolishes LXR target gene expression in response to PTEN-loss. LXR deletion triggers an increased in the epithelial mesenchymal transition process and matrix metalloproteinase accumulations that could explain metastatic spreading. This work highlights LXRs as metabolic sensors that act as gatekeeper able to constrain carcinoma progression.
 
Overall design In this study, we used prostatic samples from mice invalidated for PTEN and/or LXRalpha and LXRbeta and corresponding control samples in order to performed a comprehensive transcriptomic analysis of molecular mechanisms involved in mouse prostate carcinogenesis.
 
Contributor(s) BARON S
Citation missing Has this study been published? Please login to update or notify GEO.
Submission date Mar 13, 2017
Last update date Feb 21, 2018
Contact name silvere BARON
E-mail(s) silvere.baron@uca.fr
Phone +33473407412
Organization name Université Clermont Auvergne
Department Endocrine, Signaling and Cancer
Lab GReD
Street address 10 avenue Blaise Pascal
City AUBIERE
ZIP/Postal code 63178
Country France
 
Platforms (1)
GPL16570 [MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version]
Samples (12)
GSM2535336 WT1_SBN_23
GSM2535337 WT2_SBN_25
GSM2535338 WT3_SBN_26
Relations
BioProject PRJNA378987

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE96545_RAW.tar 105.9 Mb (http)(custom) TAR (of CEL)
GSE96545_log2_rma_annotations.txt.gz 8.2 Mb (ftp)(http) TXT
Processed data included within Sample table
Processed data are available on Series record

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