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| Status |
Public on Dec 01, 2009 |
| Title |
Global gene expression analysis in Stat3deltaIEC APCMin/+ mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Background and aims: The transcription factor Stat3 has been considered to promote progression and metastasis of intestinal cancers.
Methods: We investigated the role of Stat3 in intestinal tumors using mice with conditional ablation of Stat3 in intestinal epithelial cells (Stat3deltaIEC).
Results: In the APCmin mouse model of intestinal cancer, genetic ablation of Stat3 reduced the multiplicity of early adenomas. However, loss of Stat3 promoted tumor progression at later stages leading to formation of invasive carcinomas which significantly shortened the lifespan of Stat3deltaIEC APCmin/+ mice. Interestingly, loss of Stat3 in tumors of APCmin/+ mice had no significant impact on cell survival and angiogenesis but promoted cell proliferation. A genome-wide expression analysis of Stat3-deficient tumors suggested that Stat3 negatively regulates intestinal cancer progression via the cell adhesion molecule Ceacam1.
Conclusions: Our data suggest that Stat3 impairs progression of intestinal tumors. Therefore, detrimental effects on tumor progression have to be considered upon therapeutic targeting of the Stat3 signaling pathway in intestinal cancer.
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| Overall design |
Stat3 has been implicated in initiation of azoxymethane/dextransulfate-induced colorectal tumors of mice and is considered to promote intestinal tumor progression in humans.
We addressed the question if Stat3 is required for intestinal tumor progression in the APCmin mouse model. we established a conditional mouse model to investigate tumor formation after ablation of Stat3. For that purpose, mice with floxed Stat3 alleles were crossed to transgenic mice expressing the Cre-recombinase under control of the Villin promoter with resulting Villin-cre Stat3flox/flox (Stat3deltaIEC) mice.For tumor induction, Stat3deltaIEC mice were bred into the tumor-prone genetic background of APCmin mice. The APCmin mutation causes aberrant activation of the Wnt signaling pathway and induces tumor formation predominantly in the small intestine23. We analysed early and late stage tumorigenesis in male and female Stat3flox/flox APCmin/+ and Stat3deltaIEC APCmin/+ mice.
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| Contributor(s) |
Musteanu M, Bilban M, Eferl R |
| Citation(s) |
19962983 |
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| Submission date |
Aug 27, 2009 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Martin Bilban |
| E-mail(s) |
[email protected]
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| Phone |
++43 (0)1 40400 6441
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| Organization name |
Medical University of Vienna
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| Department |
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| Street address |
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| City |
Vienna |
| ZIP/Postal code |
1090 |
| Country |
Austria |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA117899 |
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