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Series GSE15943 Query DataSets for GSE15943
Status Public on Nov 01, 2009
Title Gene expression programs of histologically distinct stages of prostate carcinogenesis in Nkx3.1; Pten mutant mice
Organism Mus musculus
Experiment type Expression profiling by array
Summary Key histological and growth progression characteristics of human prostate cancer are phenocopied in mouse models that have been subjected to androgen level depletion and engineered for hemizygosity of candidate prostate cancer tumor suppressor genes Nkx3.1 and Pten. To characterize their relative transcriptomes and identify a genomic basis for their relevance to human prostate cancers, we compared mouse prostate tumors expression profiles to those from a panel of human prostate cancer isolates and to normal and benign prostates. Human prostate cancers and mouse prostate tumor models both exhibit the activation of genes associated with growth, cell cycle control, and inhibition of differentiation (CDKN2A, CDKN2B, CDKN2C, CEBPB, CEBPG, CSF1, CTSS, DMBT1, EGFR, PLCG2, PXN, SPP1, TNFSF9), and conversely, diminished expression of genes associated with normal prostate differentiation and function. All tumors also exhibit dysregulated expression of genes associated with inflammation, the disruption of prostate-associated ER stress pathways, as well as with oxidative stress, energy metabolism, cell adhesion, and stress response. Immunoinflammatory and altered cell adhesion process-associated genes exhibited prominent expression in early stage tumors. In contrast, metastatic human prostate cancer samples eliminated the expression of most immunoinflammatory-associated transcripts. Cross-species comparisons of molecular programs that are shared or distinguishing of Nkx3.1; Pten mutant mouse models and human adenocarcinomas clearly delineate core tumorigenesis programs associated with cell cycle activation and loss of differentiation. Compared to locally spreading mouse and human tumors, metastatic prostate cancer exhibits greatly reduced expression of immunoinflammatory and adhesion genes, implying that immuno-inflammatory activation may enable first stages of tumorogenesis, but suppress metastasis. These results provide a novel framework to identify stage-specific biomarkers and candidate targets for combinatorial therapeutics. The complex role of inflammation suggests a need for additional caution in countering metastasis.

Keywords: tumor stage
 
Overall design 26 Affymetrix MOE430A microarrays
 
Contributor(s) Jessen W, Aronow BJ, Abate-Shen C
Citation(s) 17909013
Submission date May 04, 2009
Last update date Jan 08, 2019
Contact name Bruce J Aronow
E-mail(s) bruce.aronow@chmcc.org
Phone 513-636-4865
Organization name Cincinnati Children's Hospital Medical Center
Street address
City Cincinnati
State/province OH
ZIP/Postal code 45229
Country USA
 
Platforms (1)
GPL339 [MOE430A] Affymetrix Mouse Expression 430A Array
Samples (26)
GSM399983 01-WT1-3577 (Normal)
GSM399984 02-WT2-3578 (Normal)
GSM399985 03-WT3-3616 (Normal)
Relations
BioProject PRJNA116995

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
GSE15943_RAW.tar 85.7 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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