RHG-CSF AFFECTS GENES INVOLVED IN MITOGEN SIGNALING AND EARLY GENE-EXPRESSION IN THE OVARIAN-CANCER CELL-LINE HEY

The ovarian adenocarcinoma cell line HEY was used as an in vitro model to study the influence of recombinant human granulocyte colony-stimul ating factor (rhG-CSF) on epithelial tumours such as ovarian cancer. S erum-starved cells were treated with rhC-CSF in a time and dose-depend ent manner, Cell proliferation, measured as cell division and DNA synt hesis, was stimulated about 40% by rhG-CSF. After harvesting, cells we re examined for the presence of G-CSF receptor (FAGS analysis and RT-P CR), as well as for expression of genes involved in mitogen signalling (ERKs, JNKs) and early gene expression (c-jun), rhG-CSF affected mito gen-activated pathways and was receptor-mediated if the G-CSF receptor was present. After rhG-CSF induction, Janus N-terminal kinases (JNK 1 and 2) were simultaneously increased in the cytosol, up to 30-fold as measured by Western blotting), whereas ERK 1 and 2 accumulated maxima lly by 2.5-fold 1 hr after rhG-CSF induction. c-Jun was up-regulated s trongly by this cytokine at the translational level. Our data suggest that rhG-CSF affects genes involved in mitogen signalling and early ge ne expression in solid tumours. We also noted the presence of G-CSF re ceptor on ovarian cancer cell lines, (C) 1998 Wiley-Liss, Inc.