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Prostaglandin E2 regulates aromatase activity and expression in human adipose stromal cells via two distinct receptor

Jeanette A Richards1, Robert W Brueggemeier

  • 1Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Ohio State University, Columbus, Ohio 43210, USA.

The Journal of Clinical Endocrinology and Metabolism
|June 6, 2003
PubMed

Insights

Prostaglandin E(2) (PGE(2)) complexly regulates aromatase in breast stromal cells. This prostaglandin influences aromatase activity and expression, potentially impacting hormone-dependent breast cancer growth.

Area of Science:

  • Biochemistry
  • Oncology
  • Endocrinology

Background:

  • Aromatase enzyme complex is crucial for estrogen biosynthesis and hormone-dependent breast cancer growth.
  • Mechanisms regulating aromatase activity and expression in breast stromal cells are not fully understood.
  • Prostaglandin E(2) (PGE(2)) is investigated as a regulator of aromatase in human breast stromal cells.

Purpose of the Study:

  • To investigate the regulation of aromatase activity and expression in human breast stromal cells by prostaglandin E(2) (PGE(2)).
  • To determine the role of EP(1), EP(2), and EP(3) prostaglandin receptors in mediating PGE(2)'s effects on aromatase.

Main Methods:

  • Utilized selective agonists and antagonists for EP(1), EP(2), and EP(3) receptors.
  • Assessed aromatase enzyme activity using a tritiated water-release assay.
  • Determined aromatase protein and mRNA expression via Western blotting and RT-PCR, respectively.

Main Results:

  • PGE(2), EP(1), and EP(2) receptor agonists significantly increased aromatase activity.
  • Corresponding antagonists decreased activity, while an EP(3) agonist inhibited PGE(2)-induced activity.
  • Changes in enzyme activity correlated with alterations in aromatase protein and mRNA expression.

Conclusions:

  • PGE(2) exerts complex regulation over aromatase activity and expression in breast stromal cells.
  • EP(1) and EP(2) receptors mediate stimulatory effects, while EP(3) mediates inhibitory effects.
  • This PGE(2)-mediated regulation of aromatase may play a role in hormone-dependent breast cancer development and progression.

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