Functional characterization of somatic point mutations of the human estrogen receptor α (hERα) in adenomyosis uteri
| Autor: | Holger Greschik, Dagmar-C. Fischer, Roland Schuele, X W Tong, Martin K. Oehler, Dirk G. Kieback |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Embryology
medicine.medical_specialty Transcription Genetic medicine.drug_class Steroid hormone receptor medicine.medical_treatment Endometriosis Uterus Estrogen receptor Electrophoretic Mobility Shift Assay Biology Transfection Protein Structure Secondary Cell Line Internal medicine Genetics medicine Animals Humans Point Mutation Adenomyosis Receptor Molecular Biology Uterine Diseases Estrogen Receptor alpha Obstetrics and Gynecology Cell Biology medicine.disease Protein Structure Tertiary DNA-Binding Proteins Steroid hormone Endocrinology medicine.anatomical_structure Amino Acid Substitution Reproductive Medicine Estrogen Female Developmental Biology |
| Zdroj: | MHR: Basic science of reproductive medicine. 10:853-860 |
| ISSN: | 1460-2407 1360-9947 |
| Popis: | Endometriosis and adenomyosis uteri are chronic, benign diseases caused by the presence of endometrial tissue in ectopic locations, e.g. peritoneal or deep inside the myometrial wall of the uterus and/or in the rectovaginal septum. Although adenomyosis might be considered as a special form of endometriosis, both conditions differ with respect to clinical symptoms and treatment. Induction of a hypo-estrogenic state alone or in combination with surgical removal of the extra-uterine lesion is mostly sufficient for treatment of peritoneal endometriosis. By contrast, adenomyosis uteri rarely responds to hormonal therapy and usually requires a hysterectomy for cure. Consequently, the role of steroid hormone receptors with respect to the aetiology of either condition is still a matter of discussion. Using PCR/single strand conformation polymorphism analysis, we identified somatic estrogen receptor (ER) alpha gene mutations in three out of 55 samples from adenomyosis uteri. Functional characterization revealed that two of the mutant ERalpha proteins display severely impaired DNA-binding and transactivation properties secondary to an altered response to estrogens or changes in epidermal growth factor-mediated ligand-independent activation. Although the exact mechanism remains unknown, we suggest that mutation-related silencing of estrogen responsiveness might render endometriotic cells resistant to hypo-estrogenic conditions thereby accounting for failure of estrogen-ablative therapy in adenomyosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|