title: rhG-CSF affects genes involved in mitogen signalling and early gene expression in the ovarian cancer cell line HEY.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynaecology, University Hospital, Freiburg, Germany. toto@frk1.ukl.uni-freiburg.de
authors.forename: T
authors.initials: T
authors.lastname: Brandstetter
authors.forename: E
authors.initials: E
authors.lastname: Ninci
authors.forename: U
authors.initials: U
authors.lastname: Falken
authors.forename: E
authors.initials: E
authors.lastname: Wagner
authors.forename: R
authors.initials: R
authors.lastname: Hess
authors.forename: T
authors.initials: T
authors.lastname: Bauknecht
mesh_terms: 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
chemical_list: 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