FGF-10 disrupts lung morphogenesis and causes pulmonary adenomas in vivo. Am J Physiol Lung Cell Mol Physiol 2001 Apr;280(4):L705-15
Date
03/10/2001Pubmed ID
11238011DOI
10.1152/ajplung.2001.280.4.L705Scopus ID
2-s2.0-0035000675 (requires institutional sign-in at Scopus site) 151 CitationsAbstract
Transgenic mice in which fibroblast growth factor (FGF)-10 was expressed in the lungs of fetal and postnatal mice were generated with a doxycycline-inducible system controlled by surfactant protein (SP) C or Clara cell secretory protein (CCSP) promoter elements. Expression of FGF-10 mRNA in the fetal lung caused adenomatous malformations, perturbed branching morphogenesis, and caused respiratory failure at birth. When expressed after birth, FGF-10 caused multifocal pulmonary tumors. FGF-10-induced tumors were highly differentiated papillary and lepidic pulmonary adenomas. Epithelial cells lining the tumors stained intensely for thyroid transcription factor (TTF)-1 and SP-C but not CCSP, indicating that FGF-10 enhanced differentiation of cells to a peripheral alveolar type II cell phenotype. Withdrawal from doxycycline caused rapid regression of the tumors associated with rapid loss of the differentiation markers TTF-1, SP-B, and proSP-C. FGF-10 disrupted lung morphogenesis and induced multifocal pulmonary tumors in vivo and caused reversible type II cell differentiation of the respiratory epithelium.
Author List
Clark JC, Tichelaar JW, Wert SE, Itoh N, Perl AK, Stahlman MT, Whitsett JAMESH terms used to index this publication - Major topics in bold
AdenomaAnimals
Animals, Newborn
Doxycycline
Embryonic and Fetal Development
Fetus
Fibroblast Growth Factor 10
Fibroblast Growth Factors
Intercellular Signaling Peptides and Proteins
Lung
Lung Neoplasms
Mice
Mice, Transgenic
Nuclear Proteins
Peptides
Protein Precursors
Proteins
Proteolipids
Pulmonary Surfactant-Associated Protein C
Pulmonary Surfactants
RNA, Messenger
Thyroid Nuclear Factor 1
Transcription Factors
Uteroglobin
