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Series GSE34839 Query DataSets for GSE34839
Status Public on Feb 28, 2012
Title Pten loss and RAS/MAPK activation cooperate to promote EMT and prostate cancer metastasis initiated from stem/progenitor cells
Organism Mus musculus
Experiment type Expression profiling by array
Summary PTEN loss or PI3K/AKT signaling pathway activation correlates with human prostate cancer progression and metastasis. However, in preclinical murine models, deletion of Pten alone fails to mimic the significant metastatic burden that frequently accompanies the end stage of human disease. To identify additional pathway alterations that cooperate with PTEN loss in prostate cancer progression, we surveyed human prostate cancer tissue microarrays and found that the RAS/MAPK pathway is significantly elevated both in primary and metastatic lesions. In an attempt to model this event, we crossed conditional activatable K-rasG12D/WT mice with the prostate conditional Pten deletion model we previously generated. Although RAS activation alone cannot initiate prostate cancer development, it significantly accelerated progression caused by PTEN loss, accompanied by epithelial-to-mesenchymal transition (EMT) and macrometastasis with 100% penitence. A novel stem/progenitor subpopulation with mesenchymal characteristics was isolated from the compound mutant prostates, which was highly metastatic upon orthotopic transplantation. Importantly, inhibition of RAS/MAPK signaling by PD325901, a MEK inhibitor, significantly reduced the metastatic progression initiated from transplanted stem/progenitor cells. Collectively, these data indicate that activation of RAS/MAPK signaling serves as a potentiating second hit to alteration of the PTEN/PI3K/AKT axis and co-targeting both pathways is highly effective in preventing the development of metastatic prostate cancers.
 
Overall design Murine mutants with prostate specific loss of Pten and K-ras activation (K-rasG12D) under regulation of the probasin promoter developed high grade, invasive prostate cancer. RNA was extracted from dissected prostate lobes from individual mutants with pathology thought to closely mimic human disease. Prostate tissue was subject to RNA extraction and hybridization on Affymetrix cDNA microarrays.
 
Contributor(s) Mulholland DJ, Naoko K, Marcus R, Allen Z, Linh TM, Jiaoti H, Martin G, Hong W
Citation(s) 22350410
Submission date Jan 04, 2012
Last update date Feb 11, 2019
Contact name Linh My Tran
E-mail(s) linhtran@ucla.edu
Organization name University of Los Angeles
Department Medicine - Pulmonary & Critical Care
Lab Dubinett Lab
Street address Box 951690, 37-131 CHS
City Los Angeles
State/province California
ZIP/Postal code 90095-1690
Country USA
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (6)
GSM856048 Pb-Cre+;PtenL/W;K-rasG12D/W, biological rep1
GSM856049 Pb-Cre+;PtenL/W;K-rasG12D/W, biological rep2
GSM856050 Pb-Cre+;PtenL/W;K-rasG12D/W, biological rep3
Relations
BioProject PRJNA150213

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
GSE34839_RAW.tar 21.7 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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