Type I Insulin-like Growth Factor Receptor Induces Pulmonary Tumorigenesis. Neoplasia (New York, N.Y.) [Neoplasia] Journal article | | Title | Type I Insulin-like Growth Factor Receptor Induces Pulmonary Tumorigenesis. | | Author(s) | Linnerth NM, Siwicky MD, Campbell CI, Watson KL, Petrik JJ, Whitsett JA, Moorehead RA | | Institution | Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada. | | Source | Neoplasia 2009 Jul; 11(7):672-82. | | Abstract | 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. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 19568412 |
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