Estrogen receptor- mediates human multidrug resistance associated protein 3 induction by 17-ethynylestradiol. Role of activator protein-1
| Autor: | Silvina Stella Maris Villanueva, Viviana A. Catania, Agostina Arias, Claudia Banchio, María Laura Ruiz, Juan Pablo Rigalli, Aldo D. Mottino, Mary Vore |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Farmacología y Farmacia
CIENCIAS MÉDICAS Y DE LA SALUD medicine.drug_class Molecular Sequence Data Estrogen receptor Biology Ethinyl Estradiol Biochemistry 03 medical and health sciences 0302 clinical medicine Activator protein 1 medicine Humans 17α-ethynylestradiol ETHYNYLESTRADIOL 030304 developmental biology Pharmacology 0303 health sciences Base Sequence Multidrug resistance-associated protein 2 c-jun MRP2 Estrogen Receptor alpha purl.org/becyt/ford/3.1 [https] Hep G2 Cells AP-1 Molecular biology Multiple drug resistance Transcription Factor AP-1 Medicina Básica Nuclear receptor ER Estrogen 030220 oncology & carcinogenesis purl.org/becyt/ford/3 [https] Multidrug Resistance-Associated Proteins |
| Zdroj: | CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET |
| Popis: | Previously, we have demonstrated that 17α-ethynylestradiol (EE) induces rat multidrug-resistance associated protein 3 (Mrp3, Abcc3) expression transcriptionally through estrogen receptor-α (ER-α) activation. We explored the effect of EE on MRP3 expression of human origin. HepG2 cells were transfected with ER-α and incubated with EE (1–10–50 μM) for 48 h. MRP3 protein and mRNA levels were measured by Western blotting and Real time PCR, respectively. EE up-regulated MRP3 protein and mRNA at 50 μM only in ER-α(+)-HepG2 cells. The in silico analysis of mrp3 promoter region demonstrated absence of estrogen response elements, but showed several Ap-1 binding sites. We further evaluated the potential involvement of the transcription factors c-JUN and c-FOS (members of Ap-1) in MRP3 up-regulation. ER-α(+) HepG2 cells were incubated with EE and c-FOS and c-JUN levels measured by Western blotting in nuclear extracts. EE up-regulated only c-JUN. Experiments of overexpression and knock-down of c-JUN by siRNA further demonstrated that this transcription factor is indeed implicated in MRP3 upregulation by EE. Co-immunoprecipitation assay demonstrated that EE induces c-JUN/ER-α interaction, and chromatin immunoprecipitation assay showed that this complex is recruited to the AP-1 binding consensus element present at the position (−1300/−1078 bp) of human mrp3 promoter. We conclude that EE induces MRP3 expression through ER-α, with recruitment of ER-α in complex with c-JUN to the human mrp3 promoter. Fil: Ruiz, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina Fil: Rigalli, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina Fil: Arias, Agostina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina Fil: Villanueva, Silvina Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina Fil: Banchio, Claudia Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; Argentina Fil: Vore, Mary. University Of Kentucky; Estados Unidos Fil: Mottino, Aldo Domingo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina Fil: Catania, Viviana Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina |
| Databáze: | OpenAIRE |
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