Normal and malignant human urothelium: in vitro effects of epidermal growth factor

Abstract

Cultures of human normal urothelial (HU) cells and transitional cell carcinoma (TCC) cell lines were tested for their ability to specifically bind and respond to epidermal growth factor (EGF). The criteria of response investigated were stimulation of growth and induction of ornithine decarboxylase (ODC) activity. All four human TCC cell lines tested were stimulated to grow by EGF (1-100 ng/ml) in a dose related fashion while only one of four HU cell cultures was similarly stimulated, and growth stimulation of this cell line occurred only at early passage. TCC and HU cells bound EGF to similar degrees with Kds of 0.86 nM for TCC and 2.54 nM for HU (P greater than 0.05) and 91637 +/- 9816 (SD) (high affinity) receptors/cell for TCC and 124275 +/- 16841 for HU (P greater than 0.10). Baseline ODC activity was statistically similar in the two TCC and the three HU cell cultures tested. However, EGF induced dose related ODC activity only in the TCC cell lines and not in any of the HU cell cultures. Thus, while both malignant and normal urothelium bind EGF equally well in vitro, only TCC responds to EGF in two parameters relevant to neoplasia: growth and induction of ODC activity.