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DNA-Binding Ability of NF-κB is Affected Differently by ERα and ERβ and Its Activation Results in Inhibition of Estrogen Responsiveness

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Abstract

Estrogenic effects involve interactions between estrogen receptors (ERs), response elements, and nuclear proteins. It is hypothesized that interaction between ER and NF-κB may affect the regulation of responsive genes. Electrophoretic mobility shift assay (EMSA) was performed to assess if the interaction of ERs and NF-κB affect their respective DNA-binding activities, and alkaline phosphatase assay was done to evaluate estrogenic activity. EMSA revealed that ERs inhibit DNA-binding of p50 and p65, whereas p50 did not impair ERα binding. Stimulation with estradiol inhibited DNA binding of NF-κB in ERα-transfected endometrial stromal cells (ESCs). Moreover, activation of NF-κB significantly decreased estrogen responsiveness of Ishikawa cells and ERα-transfected ESC. Our results suggest that ERs downregulate NF-κB-dependent gene activation by directly preventing DNA binding. However, NF-#x03BA;B-mediated inhibition of ER-dependent gene activation may be carried out indirectly rather than through a direct inhibition of ER-DNA binding. These findings offer new insight into the specific role of ERα and could eventually help in developing therapeutics for endometriosis.

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Author notes

  1. The first two authors, OG-K and GH, contributed equally to this article.

Authors and Affiliations

  1. Division of Reproductive Endocrinology, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut, 06520-8063, USA

    Ozlem Guzeloglu-Kayisli PhD, Gulden Halis MD, Sarper Taskiran MD, Umit A. Kayisli PhD & Aydin Arici MD

  2. Endometriosezentrum Berlin, Department of Obstetrics and Gynecology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany

    Gulden Halis MD

Authors
  1. Ozlem Guzeloglu-Kayisli PhD
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  2. Gulden Halis MD
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  3. Sarper Taskiran MD
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  4. Umit A. Kayisli PhD
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  5. Aydin Arici MD
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Corresponding author

Correspondence to Aydin Arici MD.

Additional information

This study was supported by a training grant to GH (Ha-3375/1-1) from the Deutsche Forschungsgemeinschaft (DFG).

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Guzeloglu-Kayisli, O., Halis, G., Taskiran, S. et al. DNA-Binding Ability of NF-κB is Affected Differently by ERα and ERβ and Its Activation Results in Inhibition of Estrogen Responsiveness. Reprod. Sci. 15, 493–505 (2008). https://doi.org/10.1177/1933719108317583

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