Early effects of high concentrations of progesterone and Mifepristone A gene expression study of endometrial cancer cells (Ishikawa) |
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| Authors: | Anne Ørbo Bjørn T. Moe Halvor Grønaas Ruth H. Paulssen |
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| Affiliation: | 1. Department of Pathology, University Hospital of North-Norway, N-9038 Tromsø, Norway;2. Department of Pathology, Institute of Medical Biology, Faculty of Medicine, University of Tromsø, N-9037 Tromsø, Norway;3. Western Geco, Oslo Technology Center, P.O. Box 234, N-1372, Norway;4. Laboratory of Molecular Medical Research and Microarray Resource Centre Tromsø (MRCT), Institute of Clinical Medicine, University of Tromsø, N-9037 Tromsø, Norway;1. Department of Oral and Maxillofacial Surgery, School of Medicine and Institute of Health Science, Gyeongsang National University, Jinju, Republic of Korea;2. OBS/Theriogenology and Biotechnology, College of Veterinary Medicine and Research Institute of Life Science, Gyeongsang National University, Jinju, Republic of Korea;3. Department of Pathology, School of Medicine, Gyeongsang National University, Jinju, Republic of Korea;4. Department of Medical Imaging, College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of Korea;5. Department of Dental Technology, Jinju Health College, Jinju, Republic of Korea;6. Department of Advanced Materials, College of Life Science and Nano Technology, Hannam University, Daejeon, Republic of Korea;1. Division of Gastroenterology, Hepatology, and Nutrition, The Children''s Hospital of Philadelphia Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania;2. Department of Pathology and Laboratory Medicine, The Children''s Hospital of Philadelphia Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania;3. Genomics and Computational Biology Graduate Group, The Children''s Hospital of Philadelphia Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania;4. Center for Applied Genomics, The Children''s Hospital of Philadelphia Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania;5. Department of Pediatrics, The Children''s Hospital of Philadelphia Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania;6. Department of Genetics, The Children''s Hospital of Philadelphia Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania;7. Department of Biostatistics and Epidemiology, The Children''s Hospital of Philadelphia Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania;8. Department of Molecular Medicine, University of Rome La Sapienza, Rome, Italy;1. Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden;2. Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden;1. Department of Obstetrics and Gynaecology, Chinese University of Hong Kong, Shatin, Hong Kong, People''s Republic of China;2. Department of Obstetrics and Gynaecology, Shenzhen People''s Hospital, Second Affiliated Hospital of Jinan University, Shenzhen, People''s Republic of China;3. Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong;4. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong;1. Department of Gynecologic Surgery, Gustave Roussy, Villejuif, France;2. Department of Medical Oncology, Gustave Roussy, Villejuif, France;3. Translational Research Lab U981, Gustave Roussy, Villejuif, France;4. Unit INSERM U 1030, Gustave Roussy, Villejuif, France;5. Université Paris-Sud (Paris XI), Le Kremlin Bicêtre, France;6. Department of Radiation Oncology, Leiden University Medical Center, Leiden, Netherlands;7. Memorial Sloan-Kettering Cancer Center, New York, NY, USA;8. Department of Obstetrics and Gynaecology, Hôpital Tenon, Paris, France;9. INSERM UMRS 938, Paris, France;10. Université Pierre et Marie Curie (Paris VI), Paris, France;1. Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan;2. Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan;3. Research Institute of Agriculture, Tokai University, Kumamoto, Japan |
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| Abstract: | Patients with endometrial hyperplasia representing preliminary stages of endometrial cancer have shown to respond to therapy in 100% of the cases when treated with levonorgestrel-impregnated intrauterine device. Anti-proliferative effect has also been reported after application of an anti-progestin impregnated intrauterine device which showed to induce endometrial atrophy. The intention of the present study was to obtain more information of novel therapeutic targets for hormonal treatment in endometrial hyperplasia and endometrial cancers. Gene expression of signaling pathways after stimulation of Ishikawa cells with high doses of progesterone (32 μM) or Mifepristone (32 μM) was performed. After using an oligo microarrays representing 24,650 human genes and 37,580 gene transcripts, 6154 genes remained after pre-processing and filtering. This resulted in a total of 993 up-regulated genes with 189 genes for progesterone and 255 genes for Mifepristone. The 550 down-regulated genes were distributed with 256 genes for progesterone, 127 genes for RU 486. The results showed that genes presenting the epidermal growth factor (EGF)/MAP-kinase pathway were significantly over-represented by progesterone treatment, whereas, by Mifepristone treatment genes involved in the p53 pathway were also up-regulated (data not shown). These genes may be interesting as potential new therapeutic targets in endometrial hyperplasia and endometrial cancer, as candidate genes for therapy response or as candidate markers for tumor progression. |
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