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 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.
Jones
H E
HE
Tenovus Cancer Research Centre, University of Wales College of Medicine, Cardiff, UK.
Dutkowski
C M
CM
Barrow
D
D
Harper
M E
ME
Wakeling
A E
AE
Nicholson
R I
RI
D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D011799:Quinazolines / Q000494:pharmacology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D011799:Quinazolines; C106485:ZM 252868; D066246:ErbB Receptors