Olfactomedin-4 Regulation by Estrogen in the Human Endometrium Requires Epidermal Growth Factor Signaling
| Autor: | Anton F.P.M. de Goeij, Gerard A.J. Dunselman, Patrick G. Groothuis, Antwan G. Ederveen, Andrea Romano, Claudia Marchetti, Cleophas M. Kyama, Jan P. G. Klomp, Rick Kamps, Hellen Dassen, Iris A. Schulkens, Bert Delvoux, Thomas D'Hooghe, Fred Dijcks, Chamindie Punyadeera |
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| Přispěvatelé: | Ondersteunend personeel CD, Obstetrie & Gynaecologie, MUMC+: MA Medische Staf Obstetrie Gynaecologie (9), Genetica & Celbiologie, Pathologie, RS: GROW - School for Oncology and Reproduction |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Endometriosis
Apoptosis Vimentin Endometrium Epidermal growth factor Granulocyte Colony-Stimulating Factor 80 and over Promoter Regions Genetic Adult Aged Aged 80 and over Cell Adhesion Cells Cultured Endometrial Neoplasms Epidermal Growth Factor Estrogens Female Humans Menstrual Cycle Middle Aged Receptor Epidermal Growth Factor Signal Transduction Tumor Suppressor Proteins 2734 Cultured ErbB Receptors medicine.anatomical_structure endometrial cancer Trefoil Factor-1 Signal transduction Receptor medicine.medical_specialty medicine.drug_class Cells Biology Pathology and Forensic Medicine Promoter Regions Genetic Internal medicine medicine Settore MED/06 - ONCOLOGIA MEDICA Endometrial cancer Cancer medicine.disease Endocrinology Settore MED/40 - GINECOLOGIA E OSTETRICIA Estrogen Cancer research biology.protein Regular Articles |
| Zdroj: | American Journal of Pathology, 177(5), 2495-2508. Elsevier Science |
| ISSN: | 2495-2508 0002-9440 |
| Popis: | Olfactomedin-4 (OLFM-4) is an extracellular matrix protein that is highly expressed in human endometrium. We have examined the regulation and function of OLFM-4 in normal endometrium and in cases of endometriosis and endometrial cancer. OLFM-4 expression levels are highest in proliferative-phase endometrium, and 17 beta-estradiol up-regulates OLFM-4 mRNA in endometrial explant cultures. Using the luciferase reporter under control of the OLFM-4 promoter, it was shown that both 17 beta-estradiol and OH-tamoxifen induce luciferase activity, and epidermal growth factor receptor-1 is required for this estrogenic response. In turn, EGF activates the OLFM-4 promoter, and estrogen receptor-alpha is needed for the complete EGF response. The cellular functions of OLFM-4 were examined by its expression in OLFM-4-negative HEK-293 cells, which resulted in decreased vimentin expression and cell adherence as well as increased apoptosis resistance. In cases of endometriosis and endometrial cancer, OLFM-4 expression correlated with the presence of epidermal growth factor receptor-1 and estrogen receptor-alpha (or estrogen signaling). An increase of OLFM-4 mRNA was observed in the endometrium of endometriosis patients. No change in OLFM-4 expression levels were observed in patients with endometrial cancer relative with controts. In conclusion, cross-talk between estrogen and EGF signaling regulates OLFM-4 expression. The role of OLFM-4 in endometrial tissue remodeling before the secretory phase and during the predisposition and early events in endometriosis can be postulated but requires additional investigation. (Am J Pathol 2010, 177:2495-2508: DOI: 10.2353/ajpath.2010.100026 |
| Databáze: | OpenAIRE |
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