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Characterization of mouse urothelial cell lines in different phases of transitional‐cell carcinogenesis
Author(s) -
De Boer W. I.,
Rebel J. M. J.,
Foekens J. A.,
Vermey M.,
Van Der Kwast T. H.
Publication year - 1993
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910540627
Subject(s) - carcinogenesis , biology , cell culture , cell growth , epidermal growth factor , growth factor , cell , microbiology and biotechnology , cancer research , growth factor receptor , cell cycle , receptor , signal transduction , cancer , genetics
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, karyotyp‐ing, 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, TGFα, bFGF and aFGF. This stimulation can be abolished in g/G but not in NUC‐5 cells by simultaneous addition of TGFβ. 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 tumori‐genic 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‐1 cells are aneuploid, tumorigenic, and growth‐factor‐independent. These urothelial cell lines provide a suitable tool for further studies in transitional‐cell carcinogenesis.