Differential regulation of steroid nuclear receptor coregulator expression between normal and neoplastic prostate epithelial cells
- 17 February 2010
- journal article
- research article
- Published by Wiley in The Prostate
- Vol. 70 (9), 959-970
- https://doi.org/10.1002/pros.21130
Abstract
BACKGROUND Deregulated androgen receptor (AR) action is critical for prostate cancer (PCa) progression. Aberrant expression of AR‐associated coregulators contributes to AR activity in PCa. The mechanisms underlying coregulator expression in PCa are under intense investigation as they may lead to alternative means of targeting AR activity in PCa cells. We have recently shown that over 30% of coregulator expression in the PCa cell line LNCaP is subject to androgen regulation. METHODS Using multiple PCa cell lines as well as xenograft models, non‐malignant prostate epithelial cell lines and androgen‐responsive tissues derived from a male Wistar rat model system, we explored the effect of androgen stimulation and androgen deprivation on the expression of the core coactivators SRC1, SRC2, SRC3, CBP, and p300. RESULTS Androgen stimulation of model systems representing PCa led to a decrease in the expression of SRC1, SRC2, SRC3, CBP, and p300, whereas androgen deprivation induced the expression of these coactivators. In contrast, expression of these coregulators remained largely unaffected following changes in the androgenic milieu in AR‐positive models representing non‐malignant prostate cells and tissues. CONCLUSIONS Our data indicate differences in the regulation of coregulator expression between neoplastic and normal prostate cells. These findings emphasize the important potential of targeting the mechanisms regulating coregulator expression for therapeutic intervention in PCa. Prostate 70: 959–970, 2010.Keywords
Funding Information
- NIH (CA121277, CA91956, CA15083, CA125747, DK65236)
- T.J. Martell Foundation
- Charlotte Geyer Foundation
- Belgian-American Educational Foundation
This publication has 37 references indexed in Scilit:
- Development of a Second-Generation Antiandrogen for Treatment of Advanced Prostate CancerScience, 2009
- Androgen-Induced Coactivator ANCCA Mediates Specific Androgen Receptor Signaling in Prostate CancerCancer Research, 2009
- Androgen Modulation of Coregulator Expression in Prostate Cancer CellsMolecular Endocrinology, 2009
- Expression and significance of androgen receptor coactivators in urothelial carcinoma of the bladderEndocrine-Related Cancer, 2009
- Targeting the androgen receptor pathway in prostate cancerCurrent Opinion in Pharmacology, 2008
- Nuclear receptor interaction protein, a coactivator of androgen receptors (AR), is regulated by AR and Sp1 to feed forward and activate its own gene expression through AR protein stabilityNucleic Acids Research, 2007
- Androgen Deprivation Increases p300 Expression in Prostate Cancer CellsCancer Research, 2007
- Hey1, a Mediator of Notch Signaling, Is an Androgen Receptor CorepressorMolecular and Cellular Biology, 2005
- LuCaP 35: A new model of prostate cancer progression to androgen independenceThe Prostate, 2003
- A mutation in the ligand binding domain of the androgen receptor of human INCaP cells affects steroid binding characteristics and response to anti-androgensBiochemical and Biophysical Research Communications, 1990