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

• Published in: Endocrinology (Philadelphia) Vol. 137; no. 12; pp. 5739 - 5742
• Main Authors: Zhao, Y, Agarwal, V R, Mendelson, C R, Simpson, E R
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01-12-1996
• Subjects: Adipose Tissue - metabolism; Adipose Tissue - pathology; Aromatase; Aromatase - genetics; Aromatase - metabolism; Biosynthesis; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Bucladesine - pharmacology; Colforsin - pharmacology; Cyclic AMP; Cyclic AMP - metabolism; Dinoprostone - physiology; Epithelial cells; Epithelium; Estrogens; Estrogens - biosynthesis; Female; Gene Expression Regulation; Humans; Macrophages; Promoter Regions, Genetic; Prostaglandin E2; Protein kinase A; Protein kinase C; Stromal Cells - metabolism; Tetradecanoylphorbol Acetate - pharmacology; Tumors
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/endo.137.12.8940410

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.