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Status |
Public on Dec 23, 2009 |
Title |
Specificity for the Nature of Inflammation in Lung Cancer Promotion in Mice |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
A large amount of epidemiologic data supports a role for chronic inflammation in epithelial carcinogenesis. In the lung, several studies have found that smokers with chronic obstructive pulmonary disease (COPD), an inflammatory disease of the airways and alveoli, have an increased risk of lung cancer (1.3 to 4.9 fold) compared to smokers without COPD. We have also shown that COPD-like airway inflammation induced by an aerosolized lysate of non-typeable Hemophilus influenzae (NTHi) promotes lung cancer in a Clara cell-targeted K-ras mutant mouse model (CC-LR) of lung cancer. In contrast, existing epidemiologic data suggest that allergic inflammation of the airways may be protective against lung cancer. We tested this association in a mouse model of allergic airway inflammation. CC-LR mice were sensitized to ovalbumin by intraperitoneal injection weekly for two weeks, then challenged for 30 min to an aerosol of ovalbumin in 0.9% saline weekly for eight weeks. This resulted in eosinophilic lung inflammation associated with increased levels of T helper 2 (Th2) cytokines and mucous metaplasia of airway epithelium, similar to what is seen in asthma patients. However, consistent with epidemiologic data, this type of inflammation did not result in any significant differences in lung surface tumor number (22 ± 3 in OVA exposed vs 26 ± 6 in control mice). We conclude that asthma-like (Th2) inflammation does not promote lung carcinogenesis in a Ras-initiated background, and demonstrate a clear specificity for the nature of inflammation in lung cancer promotion. These findings will assist in determination of the essential cells and signaling events in lung cancer promotion by inflammation.
Keywords: lung, chonic inflammation, microarray
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Overall design |
Wildtype or CC-LR (a Clara cell-targeted K-ras mutant mouse model of lung cancer) mice were either challenged with an aerosol of an NTHi lysate or to an aerosol of ovalbumin for eight weeks, and microarray analysis was performed on whole lung homogenates from mice on the first day after the 8th exposure.
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Contributor(s) |
Moghaddam SJ, Evans SE |
Citation(s) |
21098042 |
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Submission date |
Dec 22, 2009 |
Last update date |
Jun 14, 2018 |
Contact name |
Scott E Evans |
E-mail(s) |
[email protected]
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Organization name |
University of Texas-M.D. Anderson Cancer Center
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Department |
Pulmonary Medicine - Unit 1462
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Street address |
1400 Holcombe Blvd
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City |
Houston |
State/province |
TX |
ZIP/Postal code |
77030 |
Country |
USA |
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Platforms (1) |
GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
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Samples (24)
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Relations |
BioProject |
PRJNA122441 |