Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Effects of HIF-1α/VP16 Hybrid Transcription Factor on Estrogen Receptor in MCF-7 Human Breast Cancer Cells

  • Cho, Jung-Yoon (College of Life Science, Institute of Biotechnology, Department of Bioscience and Biotechnology, Sejong University) ;
  • Park, Mi-Kyung (College of Life Science, Institute of Biotechnology, Department of Bioscience and Biotechnology, Sejong University) ;
  • Lee, Young-Joo (College of Life Science, Institute of Biotechnology, Department of Bioscience and Biotechnology, Sejong University)
  • Published : 2005.12.01
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Abstract

The estrogen receptor (ER) is activated and degraded by estrogen. We have examined ER downregulation and activation under hypoxia mimetic conditions. Cobalt chloride induced ER downregulation at 24 h of treatment. This degradation involved hypoxia-inducible factor-1$\alpha$ (HIF-1$\alpha$) as examined by using a constitutively active form of HIF-1$\alpha$, HIF-1$\alpha$/VP16, constructed by replacing the transactivation domain of HIF-1$\alpha$ with that of VP16. Western blot analysis revealed that E2-induced ER downregulation was observed within ${\~}6h$, whereas HIF-1$\alpha$/VP16-induced ER degradation was observed within 12${\~}$20h. HIF-1$\alpha$/VP16 activated the transcription of estrogen-responsive reporter gene in the absence of estrogen. These results suggest that ER downregulation and activation under hypoxia maybe mediated in part by a HIP-1$\alpha$ expression.

Keywords

References

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