PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of bmcgenoBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Genomics
 
BMC Genomics. 2009; 10: 615.
Published online Dec 17, 2009. doi:  10.1186/1471-2164-10-615
PMCID: PMC2805698
Mouse gastric tumor models with prostaglandin E2 pathway activation show similar gene expression profiles to intestinal-type human gastric cancer
Hiraku Itadani,1 Hiroko Oshima,2 Masanobu Oshima,2 and Hidehito Kotanicorresponding author1,3
1Oncology Research Department, Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd, Tsukuba, Japan
2Division of Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan
3Presidents's Office and Business Development, Banyu Pharmaceutical Co., Ltd, Tokyo, Japan
corresponding authorCorresponding author.
Hiraku Itadani: hiraku_itadani/at/mail1.accsnet.ne.jp; Hiroko Oshima: hoshima/at/kenroku.kanazawa-u.ac.jp; Masanobu Oshima: oshimam/at/kenroku.kanazawa-u.ac.jp; Hidehito Kotani: hidehito_kotani/at/merck.com
Received April 13, 2009; Accepted December 17, 2009.
Abstract
Background
Gastric cancers are generally classified into better differentiated intestinal-type tumor and poorly differentiated diffuse-type one according to Lauren's histological categorization. Although induction of prostaglandin E2 pathway promotes gastric tumors in mice in cooperation with deregulated Wnt or BMP signalings, it has remained unresolved whether the gastric tumor mouse models recapitulate either of human gastric cancer type. This study assessed the similarity in expression profiling between gastric tumors of transgenic mice and various tissues of human cancers to find best-fit human tumors for the transgenic mice models.
Results
Global expression profiling initially found gastric tumors from COX-2/mPGES-1 (C2mE)-related transgenic mice (K19-C2mE, K19-Wnt1/C2mE, and K19-Nog/C2mE) resembled gastric cancers among the several tissues of human cancers including colon, breast, lung and gastric tumors. Next, classification of the C2mE-related transgenic mice by a gene signature to distinguish human intestinal- and diffuse-type tumors showed C2mE-related transgenic mice were more similar to intestinal-type compared with diffuse one. We finally revealed that induction of Wnt pathway cooperating with the prostaglandin E2 pathway in mice (K19-Wnt1/C2mE mice) further reproduce features of human gastric intestinal-type tumors.
Conclusion
We demonstrated that C2mE-related transgenic mice show significant similarity to intestinal-type gastric cancer when analyzed by global expression profiling. These results suggest that the C2mE-related transgenic mice, especially K19-Wnt1/C2mE mice, serve as a best-fit model to study molecular mechanism underlying the tumorigenesis of human gastric intestinal-type cancers.
Articles from BMC Genomics are provided here courtesy of
BioMed Central