title: Down-regulation of DcR2 sensitizes androgen-dependent prostate cancer LNCaP cells to TRAIL-induced apoptosis.
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.
authors.affiliation: UMR Inserm U1052/CNRS 5286, Centre Léon Bérard, 28 rue Laënnec, 69373 Lyon Cedex 08, France.
authors.forename: David
authors.initials: D
authors.lastname: Vindrieux
authors.affiliation: NYU Langone Medical Center, Department of Medicine and Pathology, 423 East 23 rd street, New York, NY 10010, USA.
authors.forename: Marie
authors.initials: M
authors.lastname: Réveiller
authors.affiliation: Inserm, retired.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Chantepie
authors.affiliation: Unité de nutrition humaine, UMR INRA U1019/Université Clermont 1, Centre de recherche INRA de Clermont-Ferrand/Theix, 63122 St Genès Champanelle, France.
authors.forename: Sadok
authors.initials: S
authors.lastname: Yakoub
authors.affiliation: U851 Inserm-UCBL-HCL, Tour INSERM CERVI, 21 avenue Tony Garnier, 69365 Lyon, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Deschildre
authors.affiliation: Service d'Urologie, Centre Hospitalier Lyon Sud, 165 chemin du grand Revoyet, 69921 Oullins, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Ruffion
authors.affiliation: Service d'Urologie, Centre Hospitalier Lyon Sud, 165 chemin du grand Revoyet, 69921 Oullins, France.
authors.forename: Marian
authors.initials: M
authors.lastname: Devonec
authors.affiliation: U895 Inserm, Université de Nice-Sophia Antipolis, UFR Medecine, 151 route Saint Antoine de Ginestiere, 06204 Nice, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Benahmed
authors.affiliation: SF Biosciences Gerland-Lyon Sud, CNRS UMS3444/Inserm US8, Université Claude Bernard Lyon 1, 50 avenue Tony Garnier, 69366 Lyon, France.
authors.forename: Renée
authors.initials: R
authors.lastname: Grataroli