FGF-10 disrupts lung morphogenesis and causes pulmonary adenomas in vivo

Transgenic mice in which fibroblast growth factor (FGF)-10 was expressed in the lungs of fetal and postnatal mice were generated with a doxycycline-in ducible system controlled by surfactant protein (SP) C or Clara cell secret ory protein (CCSP) promoter elements. Expression of FGF-10 mRNA in the feta l lung caused adenomatous malformations, perturbed branching morphogenesis, and caused respiratory failure at birth. When expressed after birth, FGF-1 0 caused multifocal pulmonary tumors. FGF10-induced tumors were highly diff erentiated papillary and lepidic pulmonary adenomas. Epithelial cells linin g the tumors stained intensely for thyroid transcription factor (TTF)-1 and SP-C but not CCSP, indicating that FGF-10 enhanced differentiation of cell s to a peripheral alveolar type II cell phenotype. Withdrawal from doxycycl ine 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 mo rphogenesis and induced multifocal pulmonary tumors in vivo and caused reve rsible type II cell differentiation of the respiratory epithelium.