EXPRESSION AND FUNCTIONS OF EGF, FGF AND TGF-BETA-GROWTH-FACTOR FAMILY MEMBERS AND THEIR RECEPTORS IN INVASIVE HUMAN TRANSITIONAL-CELL-CARCINOMA CELLS

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 transiti onal-cell carcinomas (TCC), enhanced expression of TGF alpha and EGF r eceptors correlated with an aggressive phenotype, However, little is k nown about functions of these growth factors in invasive TCCs. In this study, we performed protein- and RNA-expression studies on a set of g rowth factors and their receptors on the newly established invasive hu man TCC cell line designated 1207. The data were correlated with funct ional proliferation and migration studies. Similar expression patterns of many cellular markers, growth factors and their receptors were not ed both in the original TCC tissue and in its derivative cell line, in dicating the relevance of this cell line to the investigation of growt h factor functions on TCC cells, The proliferation induction by EGF, T GF alpha, amphiregulin, heregulin alpha, FGF-I and FGF-7 correlated wi th the presence of EGF receptors, c-erbB4 and FGFR2 (IIIb), respective ly, Amphiregulin and heregulin alpha induced the most proliferation, i n conformity with the low expression of TGF beta receptors I and II, T GF beta(1) barely inhibited proliferation, while TGF alpha induced inv asion of 1207 cells into Matrigel. These data support the notion that notably EGF-like proteins mediate TCC growth and invasion through auto crine pathways which can be reinforced by loss of TGF beta(1) regulati on. (C) 1997 Wiley-Liss, Inc.