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| Status |
Public on Jan 28, 2011 |
| Title |
Promotion of Lung Tumorigenesis By Beta-catenin |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Although mutations in Kras are present in 21% of lung tumors, there is a high level of heterogeneity in phenotype and outcomes amongst lung cancer patients suggesting the importance of other pathways. Wnt/β-catenin signaling is a known oncogenic pathway that plays a well defined role in colon and skin cancer but its role in lung cancer remains unclear. We show that activation of Wnt/β-catenin in the bronchiolar epithelium of the adult lung does not promote tumor development by itself. However, activation of Wnt/β- catenin signaling leads to a dramatic increase in tumor formation both in overall tumor number and size compared to KrasG12D alone. We show that activation of Wnt/β- catenin signaling significantly alters the KrasG12D tumor phenotype resulting in a phenotypic switch from bronchiolar epithelium to the highly proliferative distal progenitors found in the embryonic lung. This is associated with a decrease in E- cadherin expression at the cell surface which may increase metastasis in Wnt/β-catenin signaling positive tumors. Together, these data suggest that activation of Wnt/β-catenin signaling in combination with other oncogenic pathways in lung epithelium may lead to a more aggressive phenotype due to the imposition of an embryonic distal progenitor phenotype accompanied by decreased E-cadherin expression.
We performed microarray analysis of control murine lung, CC10-cre:KrasG12D, and CC10-cre:Ctnnb1ex3flox:LSL-KrasG12D double mutant micro-dissected murine lung tumors to determine their transcriptional phenotype.
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| Overall design |
Lungs of five-month-old mice were PBS inflated and all the tumors in each lobe were dissected. The total number of tumors obtained from three out of the 5 pulmonar lobes of each animal was called a sample the other two lobes were saved in case there were problems and the array needed to be repeated. Trizol was used to isolate RNA for microarray analysis. Samples & Genotypes: control murine lung n=2 animals, CC10-cre:KrasG12D n=2 animals, and CC10-cre:Ctnnb1ex3flox:LSL-KrasG12D n=2 animals.
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| Contributor(s) |
Pacheco-Pinedo EC, Durham A, Stewart KM, Goss AM, Lu MM, DeMayo FJ, Morrisey EE |
| Citation(s) |
21490395 |
| |
| Submission date |
Jan 25, 2011 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Eugenia Cristina Pacheco-Pinedo |
| E-mail(s) |
[email protected], [email protected]
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| Phone |
2677605922
|
| Fax |
2155732094
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| URL |
http://www.med.upenn.edu/morriseylab/
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| Organization name |
University of Pennsylvania
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| Department |
Department of Medicine - Cardiovascular Institute - Institute for Regenerative Medicine
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| Lab |
Morrisey Lab
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| Street address |
421 Curie Boulevard
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| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
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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 (6)
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| GSM661018 |
Lung tumor Ctnnb1ex3flox:LSL-KrasG12D double mutant rep1 |
| GSM661019 |
Lung tumor Ctnnb1ex3flox:LSL-KrasG12D double mutant rep2 |
| GSM661020 |
Lung tumor CC10-cre:KrasG12D single mutant rep1 |
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| Relations |
| BioProject |
PRJNA135971 |
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