AI Article Synopsis
- Dysregulation of apoptotic genes and androgens is crucial for the development and treatment of prostate cancer, with specific signaling pathways linked to hormone concentrations affecting cell sensitivity to TRAIL-induced apoptosis.
- Research indicates that in androgen-sensitive LNCaP prostate cancer cells, the presence of androgens influences the expression of the decoy receptor DcR2 and the pro-apoptotic receptor DR5, impacting their susceptibility to TRAIL-mediated cell death.
- Reducing DcR2 levels through siRNA resulted in increased TRAIL-induced apoptosis, highlighting the potential for targeting DcR2 expression in clinical treatments for advanced prostate tumors.
Article Abstract
Background: Dysregulation of many apoptotic related genes and androgens are critical in the development, progression, and treatment of prostate cancer. The differential sensitivity of tumour cells to TRAIL-induced apoptosis can be mediated by the modulation of surface TRAIL receptor expression related to androgen concentration. Our previous results led to the hypothesis that downregulation of TRAIL-decoy receptor DcR2 expression following androgen deprivation would leave hormone sensitive normal prostate cells vulnerable to the cell death signal generated by TRAIL via its pro-apoptotic receptors. We tested this hypothesis under pathological conditions by exploring the regulation of TRAIL-induced apoptosis related to their death and decoy receptor expression, as also to hormonal concentrations in androgen-sensitive human prostate cancer, LNCaP, cells.
Results: In contrast to androgen-insensitive PC3 cells, decoy (DcR2) and death (DR5) receptor protein expression was correlated with hormone concentrations and TRAIL-induced apoptosis in LNCaP cells. Silencing of androgen-sensitive DcR2 protein expression by siRNA led to a significant increase in TRAIL-mediated apoptosis related to androgen concentration in LNCaP cells.
Conclusions: The data support the hypothesis that hormone modulation of DcR2 expression regulates TRAIL-induced apoptosis in LNCaP cells, giving insight into cell death induction in apoptosis-resistant hormone-sensitive tumour cells from prostate cancer. TRAIL action and DcR2 expression modulation are potentially of clinical value in advanced tumour treatment.
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Source |
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3286382 | PMC |
| http://dx.doi.org/10.1186/1475-2867-11-42 | DOI Listing |
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