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Series GSE39955 Query DataSets for GSE39955
Status Public on Aug 09, 2012
Title Expression data comparing Pten-, p53-, and combined deficient mouse mammary tumors
Organism Mus musculus
Experiment type Expression profiling by array
Summary To model the effect of Pten loss on breast cancer, we deleted Pten using a floxed allele and the deleter lines MMTV-Cre(NLST), which targets stem/bi-potent progenitor cells, and WAP-Cre, which targets CD24-positive, pregnancy-identified stem cells/alveolar progenitors. Mammary tumors were detected in WAP-Cre:Ptenf/f females with a latency of 15.2 months. By 18 months, nearly all mice had succumbed to cancer. MMTV-Cre:Ptenf/f mice developed mammary tumors after a longer latency of 26.4 months and reduced penetrance (70%) compared to WAP-Cre:Ptenf/f mice. Tumors from both models were heterogeneous, consisting primarily of differentiated adenocarcinoma (adenomyoepithelioma; ~70%) and adenosquamous carcinoma (20-25%). In addition, a small fraction of tumors was classified as acinar and poorly differentiated adenocarcinoma (4-7%) and adenosarcoma (3-4%). To test the consequences of combined Pten and p53 gene mutation on breast cancer, we deleted both genes via MMTV-Cre or WAP-Cre. Kaplan-Meier tumor free survival curves revealed that WAP-Cre:Ptenf/f:p53f/f and MMTV-Cre:Ptenf/f:p53f/f females developed tumors with reduced latency of 11.3 and 9.8 months, compared with 15.2, 26.4, and 16.9 months for single-mutant WAP-Cre:Ptenf/f, MMTV-Cre:Ptenf/f or MMTV-Cre:p53f/f mice, respectively. In contrast to the heterogeneity of Pten tumors and small percentage of adenosarcomas in these mice, ~70% of Pten:p53 lesions were histologically classified as adeno-sacrcomatoid-like or mesenchymal-like breast cancer, with the rest exhibiting mixed mesenchymal plus adenocarcinomas and differentiated adenocarcinomas. The adeno-sacrcomatoid-like tumors expressed the mesenchymal markers vimentin, K5, SMA, N-cadherin and desmin but not ER, as well as islands of luminal-like K18 expressing cells surrounded by a layer of K14-positive cells.
We used microarrays to detect differentially expressed genes in the Pten:p53 double-knock-out vs Pten or p53 single deletions
 
Overall design Total RNA was extracted from tumors developed by double Trizol method and hybridized on Affymetrix microarrays.
 
Contributor(s) Liu J, Wang S, Jones R, Zacksenhaus E
Citation(s) 25330770
Submission date Aug 08, 2012
Last update date Mar 04, 2019
Contact name Jeff Liu
E-mail(s) jeff.liu@utoronto.ca
Phone 416-340-4800
Organization name University Health Network
Department Princess Margaret Cancer Center
Lab Zadeh Lab
Street address 101 College Street, RM 4-601
City Toronto
State/province Ontario
ZIP/Postal code M5G 1L7
Country Canada
 
Platforms (1)
GPL6246 [MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version]
Samples (42)
GSM982192 MMTV-Neu primary tumor N222
GSM982193 MMTV-Neu primary tumor N240
GSM982194 MMTV-Neu primary tumor N242
Relations
BioProject PRJNA172163

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Supplementary file Size Download File type/resource
GSE39955_RAW.tar 183.1 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
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