Selective transcriptional regulation of aromatase gene by vitamin D, dexamethasone, and mifepristone in human glioma cells.
The human aromatase gene (CYP19A1) is controlled by multiple promoters that give rise to different aromatase transcripts. Its regulation has been studied in cells from multiple origins, including placenta, bone, adipose tissue, and breast cancer. However, little is known about its regulation in cells from neural origin. We assessed whether vitamin D, dexamethasone, and the glucocorticoid receptor antagonist mifepristone regulate the aromatase gene in human glioma, neuroblastoma, and breast cancer cells. The results show that these compounds enhance the activity of different aromatase promoters in glioma cells, but not in neuroblastoma and breast cancer cells. Vitamin D increased the expression of I.3, I.7, and I.4 aromatase transcripts and induced de novo expression of the I.6 transcript; dexamethasone increased the expression of I.4, PII, and I.3 transcripts and mifepristone increased the expression of PII and I.3 aromatase transcripts. The cell specific regulation of CYP19A1 by vitamin D, dexamethasone, and mifepristone opens the possibility for cellular selective modulation of estrogen biosynthesis within the brain.
Yague
Josue G
JG
Instituto Cajal, CSIC, Avenida Doctor Arce 37, 28002 Madrid, Spain.
Garcia-Segura
Luis M
LM
Azcoitia
Iñigo
I
D001141:Aromatase / Q000235:genetics*; D001943:Breast Neoplasms / Q000201:enzymology; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005910:Glioma / Q000201:enzymology*; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology*; D009447:Neuroblastoma / Q000201:enzymology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D014158:Transcription, Genetic / Q000187:drug effects; D014807:Vitamin D / Q000494:pharmacology*
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D014807:Vitamin D; D015735:Mifepristone; D003907:Dexamethasone; D001141:Aromatase