Human insulin-like growth factor-IA expression in transgenic mice promotes adenomatous hyperplasia but not pulmonary fibrosis.
Insulin-like growth factor-I (IGF-I) has been implicated in postnatal 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 surfactant protein C promoter. We determined the effect of pulmonary overexpression of human IGF-IA on 1) pulmonary inflammation and fibrosis in response to intratracheal instillation of bleomycin, 2) premalignant pulmonary adenomatous hyperplasia, and 3) 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 nontransgenic 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 mo) significantly increased the incidence of premalignant adenomatous hyperplastic lesions compared with littermate controls without affecting adenoma formation. These findings suggest that increased expression of human IGF-IA in alveolar air spaces does not affect the development of pulmonary fibrosis but promotes premalignant changes in the alveolar epithelium.
Frankel
Stephen K
SK
Program in Cell Biology, Department of pediatrics, National Jewish Medical and Research Center, 1400 Jackson St., Denver, CO 80206, USA.
Moats-Staats
Billie M
BM
Cool
Carlyne D
CD
Wynes
Murry W
MW
Stiles
Alan D
AD
Riches
David W H
DW
D000236:Adenoma / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D000903:Antibiotics, Antineoplastic; D001761:Bleomycin; D005347:Fibroblasts / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D006965:Hyperplasia; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008175:Lung Neoplasms / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D011014:Pneumonia / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D011230:Precancerous Conditions / Q000473:pathology / Q000503:physiopathology*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*
D000903:Antibiotics, Antineoplastic; D001761:Bleomycin; D007334:Insulin-Like Growth Factor I