Type I Insulin-like Growth Factor Receptor Induces Pulmonary Tumorigenesis
Despite the type I insulin-like growth factor receptor (IGF-IR) being highly expressed in more than 80% of human lung tumors, a transgenic model of IGF-IR overexpression in the lung has not been created. We produced two novel transgenic mouse models in which IGF-IR is overexpressed in either lung ty...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2009-07-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558609800195 |
| _version_ | 1819058090340777984 |
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| author | Nicolle M. Linnerth Megan D. Siwicky Craig I. Campbell Katrina L.M. Watson James J. Petrik Jeffrey A. Whitsett Roger A. Moorehead |
| author_facet | Nicolle M. Linnerth Megan D. Siwicky Craig I. Campbell Katrina L.M. Watson James J. Petrik Jeffrey A. Whitsett Roger A. Moorehead |
| author_sort | Nicolle M. Linnerth |
| collection | DOAJ |
| description | Despite the type I insulin-like growth factor receptor (IGF-IR) being highly expressed in more than 80% of human lung tumors, a transgenic model of IGF-IR overexpression in the lung has not been created. We produced two novel transgenic mouse models in which IGF-IR is overexpressed in either lung type II alveolar cells (surfactant protein C [SPC]-IGFIR) or Clara cells (CCSP-IGFIR) in a doxycycline-inducible manner. Overexpression of IGF-IR in either cell type caused multifocal adenomatous alveolar hyperplasia with papillary and solid adenomas. These tumors expressed thyroid transcription factor 1 and Kruppel-like factor 5 in most tumor cells. Similar to our previous work with lung tumors that developed in the mouse mammary tumor virus-IGF-II transgenic mice, the lung tumors that develop in the SPC-IGFIR and CCSP-IGFIR transgenic mice expressed high levels of the cyclic adenosine monophosphate response element binding protein that was localized primarily to the nucleus. Although elevated IGF-IR expression can initiate lung tumor development, tumors can become independent of IGF-IR signaling as IGF-IR down-regulation in established tumors produced tumor regression in some, but not all, of the tumors. These findings implicate IGF-IR as an important initiator of lung tumorigenesis and suggest that the SPC-IGFIR and CCSP-IGFIR transgenic mice can be used to further our understanding of human lung cancer and the role IGF-IR plays in this disease. |
| first_indexed | 2024-12-21T13:49:40Z |
| format | Article |
| id | doaj.art-5493fb2364024901898e66e84156fec6 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-21T13:49:40Z |
| publishDate | 2009-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-5493fb2364024901898e66e84156fec62022-12-21T19:01:45ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022009-07-0111767268210.1593/neo.09310Type I Insulin-like Growth Factor Receptor Induces Pulmonary TumorigenesisNicolle M. Linnerth0Megan D. Siwicky1Craig I. Campbell2Katrina L.M. Watson3James J. Petrik4Jeffrey A. Whitsett5Roger A. Moorehead6Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, CanadaDepartment of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, CanadaDepartment of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, CanadaDepartment of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, CanadaDepartment of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, CanadaDepartment of Pulmonary Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH, USADepartment of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, CanadaDespite the type I insulin-like growth factor receptor (IGF-IR) being highly expressed in more than 80% of human lung tumors, a transgenic model of IGF-IR overexpression in the lung has not been created. We produced two novel transgenic mouse models in which IGF-IR is overexpressed in either lung type II alveolar cells (surfactant protein C [SPC]-IGFIR) or Clara cells (CCSP-IGFIR) in a doxycycline-inducible manner. Overexpression of IGF-IR in either cell type caused multifocal adenomatous alveolar hyperplasia with papillary and solid adenomas. These tumors expressed thyroid transcription factor 1 and Kruppel-like factor 5 in most tumor cells. Similar to our previous work with lung tumors that developed in the mouse mammary tumor virus-IGF-II transgenic mice, the lung tumors that develop in the SPC-IGFIR and CCSP-IGFIR transgenic mice expressed high levels of the cyclic adenosine monophosphate response element binding protein that was localized primarily to the nucleus. Although elevated IGF-IR expression can initiate lung tumor development, tumors can become independent of IGF-IR signaling as IGF-IR down-regulation in established tumors produced tumor regression in some, but not all, of the tumors. These findings implicate IGF-IR as an important initiator of lung tumorigenesis and suggest that the SPC-IGFIR and CCSP-IGFIR transgenic mice can be used to further our understanding of human lung cancer and the role IGF-IR plays in this disease.http://www.sciencedirect.com/science/article/pii/S1476558609800195 |
| spellingShingle | Nicolle M. Linnerth Megan D. Siwicky Craig I. Campbell Katrina L.M. Watson James J. Petrik Jeffrey A. Whitsett Roger A. Moorehead Type I Insulin-like Growth Factor Receptor Induces Pulmonary Tumorigenesis Neoplasia: An International Journal for Oncology Research |
| title | Type I Insulin-like Growth Factor Receptor Induces Pulmonary Tumorigenesis |
| title_full | Type I Insulin-like Growth Factor Receptor Induces Pulmonary Tumorigenesis |
| title_fullStr | Type I Insulin-like Growth Factor Receptor Induces Pulmonary Tumorigenesis |
| title_full_unstemmed | Type I Insulin-like Growth Factor Receptor Induces Pulmonary Tumorigenesis |
| title_short | Type I Insulin-like Growth Factor Receptor Induces Pulmonary Tumorigenesis |
| title_sort | type i insulin like growth factor receptor induces pulmonary tumorigenesis |
| url | http://www.sciencedirect.com/science/article/pii/S1476558609800195 |
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