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Series GSE25302 Query DataSets for GSE25302
Status Public on Dec 04, 2011
Title Synergistic Tumor Suppressor Activity of E-cadherin and p53 in a Conditional Mouse Model for Diffuse-Type Gastric Cancer
Organism Mus musculus
Experiment type Expression profiling by array
Summary BACKGROUND & AIMS: Gastric cancer is the second most frequent cause of death from cancer in the world, diffuse-type gastric cancer (DGC) exhibiting a poor prognosis. Germline mutations of CDH1, encoding E-cadherin, have been reported in hereditary DGCs, and genetic and/or epigenetic alterations of CDH1 are frequently detected in sporadic DGCs. Genetic alterations of TP53 are also frequently found in DGCs. To examine the synergistic effect of loss of E-cadherin and p53 on gastric carcinogenesis, we established a mouse line in which E-cadherin and p53 are specifically inactivated in the stomach parietal cell lineage. METHODS: We crossed Atp4b-Cre mice with Cdh1loxP/loxP and Trp53loxP/loxP mice, and examined the gastric phenotype of Atp4b-Cre+;Cdh1loxP/loxP;Trp53loxP/loxP mice. RESULTS: Non-polarization of E-cadherin-negative parietal cells and proton pump-negative atypical foci were observed in the transgenic mice. Intramucosal cancers and invasive cancers composed of poorly differentiated carcinoma cells and signet ring cells, which were histologically very similar to those in humans, were found from 6 and 9 months, respectively. Fatal DGCs developed at 100% penetrance within a year, frequently metastasized to lymph nodes, and had tumorigenic activity in immunodeficient mice. Gene expression profiling analyses also revealed that DGCs in the E-cadherin/p53-deficient mice resembled human DGCs. CONCLUSIONS: Our mouse line is the first genetically modified mouse model of DGC and very useful for clarifying the mechanism underlying gastric carcinogenesis, and provides a new approach to the treatment and prevention of DGC because of morphological and biochemical similarities with human DGC.
Overall design Two-condition experiment, Gastric cancer vs. normal gastric mucosal tissues. Biological replicates: pooled control sample from five normal gastric mucosal tissues, three replicates from diffuse-type gastric cancer.
Contributor(s) Shimada S, Mimata A, Mogushi K, Akiyama Y, Fukamachi H, Jonkers J, Tanaka H, Eishi Y, Yuasa Y
Citation(s) 21865403
Submission date Nov 12, 2010
Last update date Nov 01, 2017
Contact name Kaoru Mogushi
Phone +81-3-5802-1797
Organization name Juntendo University
Department Intractable Disease Research Center
Street address 2-1-1 Hongo
City Bunkyo-ku
State/province Tokyo
ZIP/Postal code 113-8421
Country Japan
Platforms (1)
GPL11202 Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version)
Samples (3)
GSM622301 Diffuse-type Gastric Cancer Replicate 1
GSM622302 Diffuse-type Gastric Cancer Replicate 2
GSM622303 Diffuse-type Gastric Cancer Replicate 3
BioProject PRJNA134787

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
GSE25302_RAW.tar 46.0 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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