The oncogenic potential of a mutant TP53 gene explored in two spontaneous lung cancer mice models
Abstract Background Lung cancer is the number one cancer killer worldwide. A major drawback in the lung cancer treatment field is the lack of realistic mouse models that replicate the complexity of human malignancy and immune contexture within the tumor microenvironment. Such models are urgently nee...
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| Format: | Article |
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BMC
2020-08-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-020-07212-6 |
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| author | Julian Ramelow Christopher D. Brooks Li Gao Abeer A. Almiman Terence M. Williams Miguel A. Villalona-Calero Wenrui Duan |
| author_facet | Julian Ramelow Christopher D. Brooks Li Gao Abeer A. Almiman Terence M. Williams Miguel A. Villalona-Calero Wenrui Duan |
| author_sort | Julian Ramelow |
| collection | DOAJ |
| description | Abstract Background Lung cancer is the number one cancer killer worldwide. A major drawback in the lung cancer treatment field is the lack of realistic mouse models that replicate the complexity of human malignancy and immune contexture within the tumor microenvironment. Such models are urgently needed. Mutations of the tumor protein p53 are among the most common alterations in human lung cancers. Methods Previously, we developed a line of lung cancer mouse model where mutant human TP53-273H is expressed in a lung specific manner in FVB/N background. To investigate whether the human TP53 mutant has a similar oncogenic potential when it is expressed in another strain of mouse, we crossed the FVB/N-SPC-TP53-273H mice to A/J strain and created A/J-SPC-TP53-273H transgenic mice. We then compared lung tumor formation between A/J-SPC-TP53-273H and FVB/N-SPC-TP53-273H. Results We found the TP53-273H mutant gene has a similar oncogenic potential in lung tumor formation in both mice strains, although A/J strain mice have been found to be a highly susceptible strain in terms of carcinogen-induced lung cancer. Both transgenic lines survived more than 18 months and developed age related lung adenocarcinomas. With micro CT imaging, we found the FVB-SPC-TP53-273H mice survived more than 8 weeks after initial detection of lung cancer, providing a sufficient window for evaluating new anti-cancer agents. Conclusions Oncogenic potential of the most common genetic mutation, TP53-273H, in human lung cancer is unique when it is expressed in different strains of mice. Our mouse models are useful tools for testing novel immune checkpoint inhibitors or other therapeutic strategies in the treatment of lung cancer. |
| first_indexed | 2024-12-13T00:12:10Z |
| format | Article |
| id | doaj.art-7d3855f9e97a42afa2bc6c08c7a8c23b |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-13T00:12:10Z |
| publishDate | 2020-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-7d3855f9e97a42afa2bc6c08c7a8c23b2022-12-22T00:05:56ZengBMCBMC Cancer1471-24072020-08-0120111010.1186/s12885-020-07212-6The oncogenic potential of a mutant TP53 gene explored in two spontaneous lung cancer mice modelsJulian Ramelow0Christopher D. Brooks1Li Gao2Abeer A. Almiman3Terence M. Williams4Miguel A. Villalona-Calero5Wenrui Duan6Department of Human & Molecular Genetics, Herbert Wertheim College of Medicine, The Florida International UniversityComprehensive Cancer Center at the Ohio State University College of MedicineDepartment of Human & Molecular Genetics, Herbert Wertheim College of Medicine, The Florida International UniversityDepartment of Human & Molecular Genetics, Herbert Wertheim College of Medicine, The Florida International UniversityComprehensive Cancer Center at the Ohio State University College of MedicineBiomolecular Sciences Institute, The Florida International UniversityDepartment of Human & Molecular Genetics, Herbert Wertheim College of Medicine, The Florida International UniversityAbstract Background Lung cancer is the number one cancer killer worldwide. A major drawback in the lung cancer treatment field is the lack of realistic mouse models that replicate the complexity of human malignancy and immune contexture within the tumor microenvironment. Such models are urgently needed. Mutations of the tumor protein p53 are among the most common alterations in human lung cancers. Methods Previously, we developed a line of lung cancer mouse model where mutant human TP53-273H is expressed in a lung specific manner in FVB/N background. To investigate whether the human TP53 mutant has a similar oncogenic potential when it is expressed in another strain of mouse, we crossed the FVB/N-SPC-TP53-273H mice to A/J strain and created A/J-SPC-TP53-273H transgenic mice. We then compared lung tumor formation between A/J-SPC-TP53-273H and FVB/N-SPC-TP53-273H. Results We found the TP53-273H mutant gene has a similar oncogenic potential in lung tumor formation in both mice strains, although A/J strain mice have been found to be a highly susceptible strain in terms of carcinogen-induced lung cancer. Both transgenic lines survived more than 18 months and developed age related lung adenocarcinomas. With micro CT imaging, we found the FVB-SPC-TP53-273H mice survived more than 8 weeks after initial detection of lung cancer, providing a sufficient window for evaluating new anti-cancer agents. Conclusions Oncogenic potential of the most common genetic mutation, TP53-273H, in human lung cancer is unique when it is expressed in different strains of mice. Our mouse models are useful tools for testing novel immune checkpoint inhibitors or other therapeutic strategies in the treatment of lung cancer.http://link.springer.com/article/10.1186/s12885-020-07212-6Lung cancerMouse modelTP53 mutationImmunotherapy |
| spellingShingle | Julian Ramelow Christopher D. Brooks Li Gao Abeer A. Almiman Terence M. Williams Miguel A. Villalona-Calero Wenrui Duan The oncogenic potential of a mutant TP53 gene explored in two spontaneous lung cancer mice models BMC Cancer Lung cancer Mouse model TP53 mutation Immunotherapy |
| title | The oncogenic potential of a mutant TP53 gene explored in two spontaneous lung cancer mice models |
| title_full | The oncogenic potential of a mutant TP53 gene explored in two spontaneous lung cancer mice models |
| title_fullStr | The oncogenic potential of a mutant TP53 gene explored in two spontaneous lung cancer mice models |
| title_full_unstemmed | The oncogenic potential of a mutant TP53 gene explored in two spontaneous lung cancer mice models |
| title_short | The oncogenic potential of a mutant TP53 gene explored in two spontaneous lung cancer mice models |
| title_sort | oncogenic potential of a mutant tp53 gene explored in two spontaneous lung cancer mice models |
| topic | Lung cancer Mouse model TP53 mutation Immunotherapy |
| url | http://link.springer.com/article/10.1186/s12885-020-07212-6 |
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