MET- - KIDNEYS EXPRESS EPITHELIAL-CELLS THAT CHEMOTAX AND FORM TUBULES IN RESPONSE TO EGF RECEPTOR LIGANDS/

The growth factor/receptor combination of hepatocyte growth factor (HG F)/c-met has been postulated to be critical for mesenchymal-to-epithel ial conversion and tubule formation in the developing kidney. We there fore isolated and immortalized cells from embryonic kidneys of met -/- transgenic mice to determine whether these cells were epithelial and able to chemotax and form tubules in vitro. The cells were immortalize d with retrovirus expressing human papillomavirus 16 (HPV 16) E6/E7 ge nes. Two rapidly dividing clones were isolated and found to express th e epithelial cell markers cytokeratin, zonula occludens-1, and E-cadhe rin but not to express the fibroblast marker vimentin. The met -/- cel ls were able to chemotax in response to epidermal growth factor and tr ansforming growth factor-alpha (TGF-alpha) and form tubules in vitro i n response to TGF-alpha but not HGF. These experiments suggest that th e HGF/c-met axis is not essential for epithelial cell development in t he embryonic kidney and demonstrate that other growth factors are capa ble of supporting early tubulogenesis.