Expression and functions of EGF FGF and TGFβ-growth-factor family members and their receptors in invasive human transitional-cell-carcinoma cells

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Abstract
Studies on epidermal‐growth‐factor‐like‐, fibroblast‐ and transforming growth factors suggested their implication in tumorigenesis involving effects on tumour‐cell proliferation and migration. In human transitional‐cell carcinomas (TCC), enchanced expression of TGFα and EGF receptors correlated with an aggressive phenotype. However, little is known about functions of these growth factors in invasive TCCs. In this study, we performed protein‐ and RNA‐expression studies on a set of growth factors and their receptors on the newly established invasive human TCC cell line designated 1207. The data were correlated with functional proliferation and migration studies. Similar expression patterns of many cellular markers, growth factors and their receptors were noted both in the original TCC tissue and in its derivative cell line, indicating the relevance of this cell line to the investigation of growth factor functions on TCC cells. The proliferation induction by EGF, TGFα, amphiregulin, heregulin α, FGF‐1 and FGF‐7 correlated with the presence of EGF receptors, c‐erbB4 and FGFR2 (IIIb), respectively. Amphiregulin and heregulin α induced the most proliferation. In conformity with the low expression of TGFβ receptors I and II, TGFβ1 barely inhibited proliferation, while TGFα induced invasion of 1207 cells into Matrigel. These data support the notion that notably EGF‐like proteins mediate TCC growth and invasion through autocrine pathways which can be reinforced by loss of TGFβ1 regulation. Int. J. Cancer 71:284–291, 1997.