| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Medicine, National Jewish Medical and Research Center, Denver, CO, USA; Department of Medicine, University of Colorado Health Sciences Center, Denver, CO, USA
2 Department of Pediatrics, University of North Carolina, Chapel Hill, NC, USA
3 Department of Medicine, National Jewish Medical and Research Center, Denver, CO, USA; Department of Pathology, University of Colorado Health Sciences Center, Denver, CO, USA
4 Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO, USA; Department of Immunology, University of Colorado Health Sciences Center, Denver, CO, USA
5 Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO, USA; Department of Medicine, National Jewish Medical and Research Center, Denver, CO, USA; Department of Immunology, University of Colorado Health Sciences Center, Denver, CO, USA
* To whom correspondence should be addressed. E-mail: richesd{at}njc.org.
Insulin-like growth factor-I (IGF-I) has been implicated in post-natal alveolar development, pulmonary fibrosis and non-small cell lung cancer. To further investigate the role of IGF-I, we created a line of transgenic mice in which alveolar type II epithelial cells express human IGF-IA under the control of the SP-C promoter. We determined the effect of pulmonary over-expression of human IGF-IA on i) pulmonary inflammation and fibrosis in response to intra-tracheal instillation of bleomycin, ii) pre-malignant pulmonary adenomatous hyperplasia and iii) adenoma formation. Transgenic expression of human IGF-IA had no effect on baseline gross lung pathology, cellularity of bronchoalveolar lavage or total lung collagen content. In addition, there were no significant differences between transgenic mice and non-transgenic littermate controls in the development of pulmonary inflammation or pulmonary fibrosis in response to intratracheal bleomycin instillation. However, pulmonary expression of human IGF-IA in older mice (> 12 months) significantly increased the incidence of pre-malignant adenomatous hyperplastic lesions compared to littermate controls without affecting adenoma formation. These findings suggest that increased expression of human IGF-IA in alveolar airspaces does not affect the development of pulmonary fibrosis, but promotes pre-malignant changes in the alveolar epithelium.
This article has been cited by other articles:
|
|
 |
|
  P. D. Ryan and P. E. Goss The Emerging Role of the Insulin-Like Growth Factor Pathway as a Therapeutic Target in Cancer Oncologist, January 1, 2008; 13(1): 16 - 24. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. P. Stabile, J. S. Lyker, S. R. Land, S. Dacic, B. A. Zamboni, and J. M. Siegfried Transgenic mice overexpressing hepatocyte growth factor in the airways show increased susceptibility to lung cancer Carcinogenesis, August 1, 2006; 27(8): 1547 - 1555. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Chua, J. Gauldie, and G. J. Laurent Pulmonary Fibrosis: Searching for Model Answers Am. J. Respir. Cell Mol. Biol., July 1, 2005; 33(1): 9 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Feghali-Bostwick IGF-I: mediator of fibrosis or carcinogenesis? Am J Physiol Lung Cell Mol Physiol, May 1, 2005; 288(5): L803 - L804. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
