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.
Zhao
Y
Y
Cecil H. and Ida Green Center for Reproductive Biology Sciences, The University of Texas Southwestern Medical Center, Dallas, USA.
Agarwal
V R
VR
Mendelson
C R
CR
Simpson
E R
ER
D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D001141:Aromatase / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone / Q000502:physiology*; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D011401:Promoter Regions, Genetic; D017154:Stromal Cells / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004967:Estrogens; D005576:Colforsin; D003994:Bucladesine; D000242:Cyclic AMP; D001141:Aromatase; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate