Estrogen biosynthesis proximal to a breast tumor is stimulated by PGE₂ via cyclic AMP, leading to activation of promoter II of the CYP19 (aromatase) gene

In the present report, we show that prostaglandin (PG) E₂ is the most potent factor which stimulates aromatase expression via cyclic AMP and promoter II. PGE₂ acts via EP₁ and EP₂ receptor subtypes to stimulate both the PKC and PKA pathways. The combined stimulation of both of these pathways results in maximal expression of promoter II-specific CYP19 transcripts. Since PGE₂ is a major secretory product both of breast tumor epithelial cells and fibroblasts, as well as of macrophages infiltrating the tumor site, then this could be the mechanism whereby estrogen biosynthesis is stimulated in breast sites adjacent to a tumor, leading in turn to increased growth and development of the tumor itself.