rhG-CSF affects genes involved in mitogen signalling 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-stimulating factor (rhG-CSF) on epithelial tumours such as ovarian cancer. Serum-starved cells were treated with rhG-CSF in a time- and dose-dependent manner. Cell proliferation, measured as cell division and DNA synthesis, was stimulated about 40% by rhG-CSF. After harvesting, cells were examined for the presence of G-CSF receptor (FACS analysis and RT-PCR), as well as for expression of genes involved in mitogen signalling (ERKs, JNKs) and early gene expression (c-jun). rhG-CSF affected mitogen-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 maximally by 2.5-fold 1 hr after rhG-CSF induction. c-Jun was up-regulated strongly by this cytokine at the translational level. Our data suggest that rhG-CSF affects genes involved in mitogen signalling and early gene expression in solid tumours. We also noted the presence of G-CSF receptor on ovarian cancer cell lines.
Brandstetter
T
T
Department of Obstetrics and Gynaecology, University Hospital, Freiburg, Germany. toto@frk1.ukl.uni-freiburg.de
Ninci
E
E
Falken
U
U
Wagner
E
E
Hess
R
R
Bauknecht
T
T
D000230:Adenocarcinoma / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics*; D011494:Protein Kinases / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000502:physiology; D011994:Recombinant Proteins; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D009419:Nerve Tissue Proteins; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D011494:Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases