Abstract | OBJECTIVES: METHODS: Human endometrial (Ishikawa, Hec-1A), ovarian (EFO-21, EFO-27, SK-OV-3), and breast cancer cell lines (MCF-7) were rendered quiescent by incubation (72 h) in the absence of fetal calf serum and phenol red. This was followed by a 15-min incubation in the absence or presence of the LHRH agonist triptorelin (100 nM) or the antagonist Cetrorelix (100 nM) before the cells were stimulated for 10 min with EGF (100 nM). C-fos mRNA expression was determined by semi-quantitative RT-PCR using a synthetic DNA fragment as internal standard. C-Fos protein synthesis was determined by SDS-PAGE and semi-quantitative Western blotting. RESULTS: In cells derived from endometrial and ovarian cancer, maximal c-fos mRNA expression (seven- to ninefold over basal level) was obtained 30 min after EGF stimulation. In the breast cancer cell line MCF-7 this effect was obtained 60 min after EGF treatment. In all of the lines expressing LHRH receptor, EGF-induced c-fos mRNA expression as well as c-Fos protein synthesis was dose-dependently reduced by treatment with LHRH agonists and antagonists. At 100 nM concentrations of the LHRH analogs, c-fos expression was reduced to baseline levels. No effect of LHRH analogs on EGF-induced c-fos expression was observed in the ovarian cancer cell line SK-OV-3, which does not express the LHRH receptor. CONCLUSIONS: These results suggest that the binding of LHRH agonists and antagonists to their receptors inhibits the mitogenic signal transduction pathway of the EGF receptor in endometrial, ovarian, and breast cancer cell lines. The coupling of both signal transduction systems mediates the antiproliferative effect of LHRH analogs.
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Authors | C Gründker, P Völker, K D Schulz, G Emons |
Journal | Gynecologic oncology
(Gynecol Oncol)
Vol. 78
Issue 2
Pg. 194-202
(Aug 2000)
ISSN: 0090-8258 [Print] United States |
PMID | 10926802
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 2000 Academic Press. |
Chemical References |
- Antineoplastic Agents, Hormonal
- Hormone Antagonists
- Luteolytic Agents
- Proto-Oncogene Proteins c-fos
- RNA, Messenger
- Receptors, LHRH
- Triptorelin Pamoate
- Gonadotropin-Releasing Hormone
- Epidermal Growth Factor
- cetrorelix
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Topics |
- Antineoplastic Agents, Hormonal
(pharmacology)
- Down-Regulation
(drug effects)
- Epidermal Growth Factor
(antagonists & inhibitors, pharmacology)
- Female
- Gene Expression
(drug effects)
- Gene Expression Regulation, Neoplastic
(drug effects)
- Genes, fos
(drug effects, genetics)
- Genital Neoplasms, Female
(genetics, metabolism)
- Gonadotropin-Releasing Hormone
(agonists, analogs & derivatives, antagonists & inhibitors, pharmacology)
- Hormone Antagonists
(pharmacology)
- Humans
- Luteolytic Agents
(pharmacology)
- Proto-Oncogene Proteins c-fos
(biosynthesis)
- RNA, Messenger
(genetics, metabolism)
- Receptors, LHRH
(physiology)
- Reverse Transcriptase Polymerase Chain Reaction
- Triptorelin Pamoate
(pharmacology)
- Tumor Cells, Cultured
(drug effects)
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