Transcriptional activation of breast cancer-associated gene 2 by estrogen receptor
| Autor: | Fathima R. Kona, Qiuzhi Cui, Daniela Buac, Luke Bisoski, Q. Ping Dou, Karri Stark |
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| Rok vydání: | 2012 |
| Předmět: |
Transcriptional Activation
Chromatin Immunoprecipitation Cancer Research medicine.drug_class Ubiquitin-Protein Ligases Estrogen receptor Breast Neoplasms Response Elements Article Estrogen Receptor Modulators Genes Reporter medicine Humans Cycloheximide Estrogen receptor beta Luciferases Renilla Protein Synthesis Inhibitors Hormone response element Gene knockdown Estradiol biology Estrogen Receptor alpha Molecular biology Ubiquitin ligase Gene Expression Regulation Neoplastic Oncology Estrogen Gene Knockdown Techniques MCF-7 Cells biology.protein Female RNA Interference Estrogen receptor alpha hormones hormone substitutes and hormone antagonists Tamoxifen Protein Binding medicine.drug |
| Zdroj: | Breast Cancer Research and Treatment. 135:495-503 |
| ISSN: | 1573-7217 0167-6806 |
| Popis: | RNF115, or Breast Cancer-Associated Gene 2 (BCA2), encodes a RING-finger ubiquitin E3 ligase, expression of which was associated with estrogen receptor (ER)-positive status in human breast tumors. Although the BCA2 promoter contains several estrogen response element (ERE) half-sites, the role of ER in the regulation of BCA2 transcription has not been reported. The aim of this study is to investigate the molecular mechanism by which estrogen regulates BCA2 transcription. BCA2 mRNA and protein levels were examined by RT-PCR and Western blot analysis, respectively, and localization was assessed by immunofluorescence. BCA2 promoter activity in response to E(2) was tested by a dual luciferase reporter assay and ER binding to the BCA2 promoter was examined by chromatin immunoprecipitation assay. We found that BCA2 mRNA and protein levels are regulated by estrogen in ER-positive MCF7 breast cancer cells and MDA MB 231 cells stably transfected with ER. Estrogen treatment in hormonal depleted MCF7 and MDA MB 231/ER stably transfected cells resulted in increased nuclear ER and cytoplasmic and nuclear BCA2 staining. Cycloheximide is not able to inhibit BCA2 mRNA levels, suggesting potential BCA2 regulation at the transcriptional level. Anti-estrogens like tamoxifen and ICI 182 178 counteracted E(2)-induced BCA2 protein and knockdown of ER by ER siRNA resulted in a significant decrease in BCA2 protein and a lower nuclear expression pattern. Estrogen treatment lead to a significant increase in BCA2 promoter response, associated with increased binding of ER to the ERE region of the BCA2 promoter. BCA2 is therefore a newly identified transcriptional target of estrogen receptor. |
| Databáze: | OpenAIRE |
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