NEW EGF-R SELECTIVE TYROSINE KINASE INHIBITOR REVEALS VARIABLE GROWTH-RESPONSES IN PROSTATE CARCINOMA CELL-LINES PC-3 AND DU-145

The effect of an EGF-R selective tyrosine kinase inhibitor ZM252868 wa s evaluated on the proliferation of PC-3 and DU-145 prostate cancer ce ll lines, which are purported to utilize an EGF-R-mediated autocrine p athway for regulation of cell growth. Basal growth of DU-145 cells was inhibited in a dose-dependent manner by the inhibitor, showing a 70% reduction at 1 mu M, whilst the growth of PC-3 cells was not affected at this concentration. In the presence of 0.1 mu M inhibitor, EGF and TGF alpha-stimulated DU-145 cell growth was decreased to below basal l evels, while only TGF alpha-stimulated PC-3 cell growth was inhibited at a 1-mu M concentration. Any growth responses to aFGF, bFGF, KGF, IG FI and PDGF by DU-145 and PC-3 cells were unaffected by the inhibitor at concentrations of 1 mu M or less. Additionally, the distribution of immunoreactive EGF-R varied between DU-145 and PC-3 cells, with EGF-R being predominately located on the cell membrane and in the cytoplasm , respectively. (C) 1997 Wiley-Liss, Inc.