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Androgen increases androgen receptor protein while decreasing receptor mRNA in LNCaP cells
A Krongrad1, C M Wilson, J D Wilson
1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-8857.
Abstract:
We have examined the effect of androgen treatment on androgen receptor mRNA and protein expression in the LNCaP human prostate carcinoma cell line. Incubation with androgen caused a decrease in cellular androgen receptor mRNA content that was concentration and time dependent. Maximal suppression to approximately 35% of control level was observed after 49 h of exposure to androgen. By contrast, incubation of LNCaP cells with androgen resulted in a 2-fold increase in the cellular content of androgen receptor protein at 24 h. At 49 h androgen receptor protein increased 30% as assayed by immunoblots and 79% as assayed by ligand binding. These results suggest that ligand-induced changes in androgen receptor stability and/or the translational efficiency of androgen receptor mRNA account for the phenomenon of androgen receptor upregulation observed in cultured LNCaP cells. Furthermore, the suppression of androgen mRNA and protein that is caused by prolonged incubation with androgen is incomplete and is reversible upon removal of ligand.
Insights
Androgen treatment decreases androgen receptor mRNA but increases androgen receptor protein in LNCaP prostate cancer cells. This suggests changes in protein stability or translation, with effects reversible upon ligand removal.
Area of Science:
- Molecular endocrinology
- Prostate cancer research
Background:
- The androgen receptor (AR) plays a crucial role in prostate cancer development and progression.
- Understanding AR regulation by androgens is vital for developing effective therapies.
Purpose of the Study:
- To investigate the impact of androgen treatment on androgen receptor (AR) mRNA and protein expression in LNCaP cells.
- To elucidate the mechanisms underlying AR expression changes in response to androgen stimulation.
Main Methods:
- LNCaP human prostate carcinoma cells were treated with varying concentrations and durations of androgen.
- Androgen receptor mRNA levels were quantified.
- Androgen receptor protein levels were assessed using immunoblotting and ligand binding assays.
Main Results:
- Androgen treatment led to a concentration- and time-dependent decrease in AR mRNA, reaching 35% of control levels after 49 hours.
- Conversely, AR protein levels increased twofold at 24 hours and by 30-79% at 49 hours.
- These findings indicate a complex regulatory response to androgen.
Conclusions:
- Ligand-induced alterations in AR protein stability and/or translational efficiency of AR mRNA likely explain AR upregulation.
- Prolonged androgen exposure results in incomplete and reversible suppression of AR mRNA and protein.
- These dynamic AR regulatory mechanisms are important in prostate cancer cell response to androgens.