CHARACTERIZATION OF MOUSE UROTHELIAL CELL-LINES IN DIFFERENT PHASES OF TRANSITIONAL-CELL CARCINOGENESIS

Altered cellular responsiveness to growth factors is one of the factors involved in carcinogenesis. In order to study the role of growth factors in transitional-cell carcinogenesis, we established 3 urothelial cell lines from normal mouse urothelium, designated g/G, NUC-5 and NUC-1. These cell lines were studied by light and transmission electron microscopy, karyotyping, grafting in syngeneic mice, growth-factor response in vitro under serum-free conditions, and EGF receptor expression. In the presence of insulin or insulin-like growth factors I and II, proliferation of the non-tumorigenic DNA-tetraploid g/G and DNA aneuploid NUC-5 cells is stimulated by EGF, TGFalpha, bFGF and aFGF. This stimulation can be abolished in g/G but not in NUC-5 cells by simultaneous addition of TGFbeta. Proliferation of g/G and NUC-5 cells can also be stimulated by PDGF-AA. The spindle-cell-like NUC-I cells are DNA aneuploid and tumorigenic in syngeneic mice; they express low levels of EGF receptors and their autonomous proliferation is only affected by insulin or insulin-like growth factors. Each of these cell lines seems to reflect a different phase in transitional-cell carcinogenesis: g/G cells have gained immortality, have become tetraploid, but are non-tumorigenic and growth-factor-dependent. NUC-5 cells have become aneuploid, have a growth-factor responsiveness different from that of normal epithelial cells, but are still non-tumorigenic. NUC-I cells are aneuploid, tumorigenic, and growth-factor-independent. These urothelial cell lines provide a suitable tool for further studies in transitional-cell carcinogenesis. (C) 1993 Wiley-Liss, Inc.