Biochemical control of breast aromatase.
Aromatase activity is increased in breast tumors and it is possible that this results from stimulation by cytokines and/or prostaglandin E2 (PGE2) which regulate the activity of this enzyme. As different promoters can be used to control aromatase gene expression in normal and malignant breast tissues, which are regulated by different factors, we are currently investigating the relative roles of cytokines and PGE2 in controlling breast tumor aromatase activity. No significant effect of PGE2 on aromatase activity in MCF-7 breast cancer cells has so far been detected. However, preliminary evidence was obtained, from co-cultures of MCF-7 cells and breast tumor-derived fibroblasts, that MCF-7 cells secrete a factor, possibly a cytokine, which can act in a paracrine manner to enhance aromatase activity in stromal cells. Understanding the complex regulation of aromatase activity in breast tumors could lead to novel therapies for specifically inhibiting tumor estrogen synthesis.
Singh
A
A
Unit of Metabolic Medicine, Imperial College School of Medicine, St. Mary's Hospital, London, UK.
Purohit
A
A
Coldham
N G
NG
Ghilchik
M W
MW
Reed
M J
MJ
D001141:Aromatase / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000201:enzymology*; D011453:Prostaglandins / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000201:enzymology
D016207:Cytokines; D011453:Prostaglandins; D001141:Aromatase