Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/119819
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Regulation of androgen receptor gene expression by steroids and retinoic acid in human breast‐cancer cells |
Author: | Hall, R.E. Tilley, W.D. McPhaul, M.J. Sutherland, R.L. |
Citation: | International Journal of Cancer, 1992; 52(5):778-784 |
Publisher: | Wiley |
Issue Date: | 1992 |
ISSN: | 0020-7136 1097-0215 |
Statement of Responsibility: | Rosemary E. Hall, Wayne D. Tilley, Michael J. McPhaul, Robert L. Sutherland |
Abstract: | Although the androgen receptor (AR) has been detected by ligand-binding assays, there is little known about the expression and regulation of the AR gene in human breast-cancer cells. AR mRNA, measured by Northern analysis in 18 cell lines, was found to be expressed predominantly in oestrogen- and progesterone-receptor-positive (ER+, PR+) lines as a single species of approximately 10.5 kb but was also comparatively abundant in I ER- and PR-negative cell line, MDA-MB-453. Dexamethasone (Dex), Organon 2058 (Org 2058), dihydrotestosterone (DHT), and all-trans-retinoic acid (RA) down-regulated AR mRNA levels in T-47D (ER+, PR+) cells 6 hr after treatment, whereas oestradiol (E2) had no effect. In MDA-MB-453 (ER-, PR-) cells, regulation of AR mRNA by RA differed from the other cell lines: RA increased the level of AR mRNA. DHT-binding assays indicated a corresponding increase in AR protein. Transfection of the androgen-responsive mouse mammary tumour virus long-terminal repeat (MMTV LTR) linked to a chloramphenicol acetyltransferase (CAT) reporter gene was used to examine the effect of altered AR levels on androgen action. The increased level of AR following RA pre-treatment in MDA-MB-453 cells resulted in enhanced induction of CAT activity by DHT and, conversely, a decrease in the level of AR following RA pretreatment in T-47D cells resulted in reduced induction of CAT activity by DHT. These data demonstrate that AR is expressed predominantly in ER+ and PR+ cell lines and its expression is regulated by ligands also known to regulate ER or PR, including progestins and retinoids. Androgen responsiveness measured by a transfected reporter gene was altered according to the extent of up- or down-regulation of AR expression, demonstrating that responsiveness is dependent on receptor concentration. |
Keywords: | Gene Expression Regulation, Neoplastic |
Rights: | © 1992 Wiley‐Liss, Inc., A Wiley Company |
DOI: | 10.1002/ijc.2910520518 |
Published version: | http://dx.doi.org/10.1002/ijc.2910520518 |
Appears in Collections: | Aurora harvest 4 Medicine publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.