Function of estrogen-related receptor alpha in human endometrial cancer
| Autor: | Hideo Honjo, Takeshi Yamaguchi, Kenichi Hosokawa, Taisuke Mori, Ai Watanabe, Yoshiyuki Kinoshita |
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| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
medicine.drug_class Endocrinology Diabetes and Metabolism Clinical Biochemistry Estrogen receptor Biology Transfection Biochemistry Estrogen-related receptor alpha Estrogen-related receptor Endocrinology Internal medicine Cell Line Tumor medicine Humans RNA Messenger Receptor Luciferases Hormone response element Reverse Transcriptase Polymerase Chain Reaction Biochemistry (medical) Estrogen Receptor alpha Glyceraldehyde-3-Phosphate Dehydrogenases Immunohistochemistry Endometrial Neoplasms Nuclear receptor Estrogen Female hormones hormone substitutes and hormone antagonists HeLa Cells Plasmids |
| Zdroj: | The Journal of clinical endocrinology and metabolism. 91(4) |
| ISSN: | 0021-972X |
| Popis: | The estrogen-related receptor alpha (ERRalpha) is an orphan member of the nuclear receptor superfamily that is closely related to estrogen receptor alpha (ERalpha). ERRalpha binds an estrogen response element (ERE), directly competes with ERalpha for binding ERE, and represses ERE-dependent transcription in MCF-7 cells, ER-positive breast cancer cells.We investigated whether ERRalpha modulate some ER-dependent activities in endometrial cancer.We investigated protein and mRNA expression of ERRalpha in endometrial cancer using immunohistochemistry and RT-PCR, respectively. After transient transfection using the ERRalpha expression vector (pCI-ERRalpha) or ERRalphaSi, which suppressed the expression of endogenous ERRalpha, Ishikawa cells were assayed for ERE-dependent luciferase activity. Cells stably overexpressing ERRalpha were generated and compared with estrogen-dependent and -independent cell growth.ERRalpha was detected in human endometrial cancer tissues by immunohistochemistry. An RT-PCR study showed that mRNA of ERRalpha was expressed in four endometrial cancer cell lines (Ishikawa, Hec1a, KLE, and SNGII) and 11 human endometrial tissues. Overexpression of ERRalpha repressed estrogen-induced ERE-dependent transcriptional activity in Ishikawa cells. After transfection with ERRalphaSi1, the expression of endogenous ERRalpha decreased to 0.5-fold, and estrogen-induced ERE luciferase activity increased to 1.5-fold. The cells stably overexpressing ERRalpha grew up more slowly than control cells in the presence of 10 nm estradiol.ERRalpha is expressed in human endometrial cancer tissues and cell lines and suppresses ERE-dependent transcriptional activity in the presence of estrogen. ERRalpha modulates estrogen-induced activity in estrogen-dependent endometrial cancer. |
| Databáze: | OpenAIRE |
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