New EGF-R selective tyrosine kinase inhibitor reveals variable growth responses in prostate carcinoma cell lines PC-3 and DU-145.

Abstract

The effect of an EGF-R selective tyrosine kinase inhibitor ZM252868 was evaluated on the proliferation of PC-3 and DU-145 prostate cancer cell lines, which are purported to utilize an EGF-R-mediated autocrine pathway 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 microM, whilst the growth of PC-3 cells was not affected at this concentration. In the presence of 0.1 microM inhibitor, EGF and TGF alpha-stimulated DU-145 cell growth was decreased to below basal levels, while only TGF alpha-stimulated PC-3 cell growth was inhibited at a 1-microM concentration. Any growth responses to aFGF, bFGF, KGF, IGF1 and PDGF by DU-145 and PC-3 cells were unaffected by the inhibitor at concentrations of 1 microM 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.

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@article{Jones1997NewES, title={New EGF-R selective tyrosine kinase inhibitor reveals variable growth responses in prostate carcinoma cell lines PC-3 and DU-145.}, author={H. E. Jones and Carol M Dutkowski and Denise Barrow and M. E. Harper and Alan E. Wakeling and Robert Ian Nicholson}, journal={International journal of cancer}, year={1997}, volume={71 6}, pages={1010-8} }