Back to Search
Start Over
Regulation of androgen receptor mRNA and protein level by steroid hormones in human mammary cancer cells.
- Source :
-
The Journal of steroid biochemistry and molecular biology [J Steroid Biochem Mol Biol] 1992 Dec; Vol. 43 (7), pp. 599-607. - Publication Year :
- 1992
-
Abstract
- The regulation of the human androgen receptor (AR) by steroid hormones in human mammary cancer cells was investigated using immunocytochemical and ligand binding assays for its protein and Northern blot analyses for the corresponding mRNA. MFM-223 cells contain high levels of ARs and are growth-inhibited by dihydrotestosterone (DHT). The AR protein is down-regulated to 57% of the control by 10 nM DHT after 24 h, and the corresponding mRNA is also reduced. The nonsteroidal antiandrogen hydroxyflutamide had no effect on the AR level, whereas after incubation with 1 microM cyproterone acetate a slight down-regulation was observed. The AR level was restored completely after release from a 7 day treatment with DHT. However, only 60% of the control level was restored, if the cells wer grown in the presence of DHT for 6 weeks. In androgen-pretreated cells the proliferation rate remained decreased even after the withdrawal of DHT. Concomitantly the distinct growth inhibition was lost. Transfection experiments demonstrated a reduced activity of the residual androgen receptor in these pretreated cells. In addition to the AR, EFM-19 cells also contain significant amounts of estrogen and progesterone receptors. EFM-19 cells are not growth inhibited by physiological concentrations of DHT. Autoregulation of AR was also found in this cell line. Additionally, reduced levels of AR protein and mRNA were found in EFM-19 cells after treatment with the synthetic progestin R5020. The maximum effect of R5020 was observed at the high concentration of 1 microM. Estrogen treatment with 10 nM 17 beta-estradiol for 3 days reduced the AR level only by 25%.
- Subjects :
- Blotting, Northern
Cyproterone pharmacology
Dihydrotestosterone pharmacology
Estradiol pharmacology
Flutamide analogs & derivatives
Flutamide pharmacology
Humans
Immunohistochemistry
Progesterone Congeners pharmacology
RNA, Messenger biosynthesis
Radioligand Assay
Receptors, Androgen biosynthesis
Tumor Cells, Cultured
Breast Neoplasms genetics
Gene Expression Regulation, Neoplastic
Hormones pharmacology
Receptors, Androgen genetics
Steroids pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0960-0760
- Volume :
- 43
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- The Journal of steroid biochemistry and molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 1472451
- Full Text :
- https://doi.org/10.1016/0960-0760(92)90284-p