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Regulation of bcl-2 transcription by estrogen receptor-α and c-Jun in human endometrium

Zhong-Lian Li1, Ken Ueki, Koji Kumagai

  • 1Department of Anatomy and Biology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.

Medical Molecular Morphology
|May 14, 2013
PubMed

Insights

Estrogen receptor alpha (ERα) regulates bcl-2 expression in the endometrium through direct DNA binding or protein interactions with c-Jun, revealing a novel menstrual cycle control mechanism.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Gynecologic Oncology

Background:

  • The estrogen-estrogen receptor (ER) pathway is vital for reproduction and implicated in breast and uterine cancers.
  • ER can regulate gene expression via estrogen-responsive elements (ERE) or protein-protein interactions.
  • Previous work linked c-Jun binding to bcl-2 promoter to proliferative phase expression.

Purpose of the Study:

  • To elucidate the mechanism of menstrual cyclic bcl-2 gene expression in the human endometrium.
  • To investigate the roles of ERα and c-Jun in regulating bcl-2 expression during the menstrual cycle.

Main Methods:

  • Analysis of ERα binding to ERE in the c-Jun promoter.
  • Investigation of ERα interaction with c-Jun bound to the bcl-2 gene promoter.
  • Detection of phosphorylated c-Jun binding to bcl-2 gene motifs.

Main Results:

  • Menstrual cyclic bcl-2 expression is regulated by ERα through either direct ERE binding on the c-Jun promoter or ERα-c-Jun interaction at the bcl-2 gene.
  • Transcriptionally active, phosphorylated c-Jun (at Ser63) binds to bcl-2 gene motifs independently of the menstrual cycle phase.
  • A novel regulatory pathway for bcl-2 transcription in the normal human endometrium was identified.

Conclusions:

  • ERα and c-Jun collaboratively regulate menstrual cyclic bcl-2 expression in the endometrium.
  • This study uncovers a new molecular mechanism controlling bcl-2 transcription in normal human endometrial tissue.
  • Understanding this pathway may offer insights into gynecologic pathologies involving aberrant bcl-2 expression.

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