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-I. 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, TGF alpha, bFGF and aFGF. This stimulation can be abolished in g/G but not in NUC-5 cells by simultaneous addition of TGF beta. 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.
De Boer
W I
WI
Department of Pathology, Erasmus University, Rotterdam, The Netherlands.
Rebel
J M
JM
Foekens
J A
JA
Vermey
M
M
Van der Kwast
T H
TH
D000818:Animals; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004847:Epithelial Cells; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D006133:Growth Substances / Q000494:pharmacology; D007633:Keratins / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D011003:Ploidies; D014551:Urinary Tract / Q000166:cytology; D014571:Urologic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
D006133:Growth Substances; D007633:Keratins; D066246:ErbB Receptors