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Cancer Cell International
Published in: Cancer Cell International 1/2011

Open Access 01-12-2011 | Primary research

Down-regulation of DcR2 sensitizes androgen-dependent prostate cancer LNCaP cells to TRAIL-induced apoptosis

Authors: David Vindrieux, Marie Réveiller, Jacqueline Chantepie, Sadok Yakoub, Catherine Deschildre, Alain Ruffion, Marian Devonec, Mohamed Benahmed, Renée Grataroli

Published in: Cancer Cell International | Issue 1/2011

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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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Metadata
Title
Down-regulation of DcR2 sensitizes androgen-dependent prostate cancer LNCaP cells to TRAIL-induced apoptosis
Authors
David Vindrieux
Marie Réveiller
Jacqueline Chantepie
Sadok Yakoub
Catherine Deschildre
Alain Ruffion
Marian Devonec
Mohamed Benahmed
Renée Grataroli
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2011
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-11-42

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