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| Status |
Public on Nov 18, 2023 |
| Title |
Tumor cells obtain and overexpress AT2 cell marker |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background: The tobacco carcinogen urethane causes lung adenocarcinomas (LUAD) in mice. They show high similarity to human LUAD of smokers, including driver KrasQ61R mutations. However, the time line of KRASQ61R mutation acquisition as well as the affected cell lineages are still obscure.
Objectives: With this study we aim to identify which cells of the lung gain KrasQ61R mutations and when they occur in response to urethane treatment.
Methods: Airway and alveolar GFP-lineage-marked mice received single urethane hits (1 g/Kg). Lungs were harvested at 0, 1, 2, 4, and 8 weeks and LUAD tumors were collected at 16, 24, and 32 weeks post-urethane. The DNA was subjected to digital droplet PCR interrogating the coexistence of GFP and KrasQ61R in the same DNA copy. RNA of tumors was submitted to sequencing for gene expression analysis.
Results: Starting from even 1 week post-urethane, both airway and alveolar lineages suffered KrasQ61R mutations (2.57% of copies examined). In airway-labelled cells KrasQ61R mutations increased by 4.06% and 2.55% at 4 and 32 weeks post-urethane, respectively. In contrast, in alveolar-labelled cells KrasQ61R mutations declined by 5.92% and 6.12%. Strikingly, gene expression analysis on tumors revealed an over expression of alveolar markers whereas expression of airway marker genes decreased.
Conclusion: After pulmonary tumor initiation by urethane, airway cells accumulate KrasQ61R mutations over time, whereas alveolar cells tend to lose them. However, tumor cells are over expressing alveolar cell markers and lose airway markers. Altogether, these results indicate that smoking-induced LUAD develops from club cells which acquire alveolar cell characteristics. These data provide further insights into the mechanisms underlying LUAD evolution in patients.
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| Overall design |
Comparison of differential gene expression between control mouse lungs and urethane induced lung tumors; triplicates are used for each group
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| Contributor(s) |
Giotopoulou GA, Behrend SJ, Stathopoulos GT |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Nov 19, 2020 |
| Last update date |
Nov 18, 2023 |
| Contact name |
Georgios T Stathopoulos |
| E-mail(s) |
stathopoulos@helmholtz-muenchen.de
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| Organization name |
Helmholz Zentrum Munich
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| Department |
Comprehensive Pneumology Center
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| Lab |
Laboratory for Molecular Respiratory Carcinogenesis
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| Street address |
Max-Lebsche-Platz
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| City |
Munich |
| State/province |
Bayern |
| ZIP/Postal code |
81377 |
| Country |
Germany |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA679553 |
| SRA |
SRP293253 |
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