Down-regulation of DcR2 sensitizes androgen-dependent prostate cancer LNCaP cells to TRAIL-induced apoptosis.
Down-regulation of DcR2 sensitizes androgen-dependent prostate cancer LNCaP cells to TRAIL-induced apoptosis.
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DOI：
10.1186/1475-2867-11-42
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发表时间：
2011-12-02
影响因子：
5.8
通讯作者：
Grataroli R
中科院分区：
文献类型：
--
作者：
Vindrieux D;Réveiller M;Chantepie J;Yakoub S;Deschildre C;Ruffion A;Devonec M;Benahmed M;Grataroli R
许多凋亡相关基因和雄激素的失调在前列腺癌的发生、发展和治疗中至关重要。肿瘤细胞对TRAIL诱导的凋亡的不同敏感性可以通过调节与雄激素浓度相关的表面TRAIL受体表达来介导。我们先前的结果导致这样的假设，即雄激素剥夺后TRAIL-诱饵受体DcR 2表达的下调将使激素敏感的正常前列腺细胞容易受到TRAIL通过其促凋亡受体产生的细胞死亡信号的影响。我们在病理条件下通过探索TRAIL诱导的细胞凋亡与其死亡和诱饵受体表达的调节以及雄激素敏感的人前列腺癌LNCaP细胞中的激素浓度来验证这一假设。与雄激素不敏感的PC 3细胞相反，诱饵（DcR 2）和死亡（DR 5）受体蛋白表达与LNCaP细胞中的激素浓度和TRAIL诱导的细胞凋亡相关。通过siRNA沉默雄激素敏感性DcR 2蛋白表达导致与LNCaP细胞中雄激素浓度相关的TRAIL介导的凋亡显著增加。这些数据支持这样的假设，即DcR 2表达的激素调节调节TRAIL诱导的LNCaP细胞凋亡，从而深入了解前列腺癌中抗凋亡敏感性肿瘤细胞的细胞死亡诱导。TRAIL作用和DcR 2表达调节在晚期肿瘤治疗中具有潜在的临床价值。
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. 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. 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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影响因子：
3.6
作者：
Rokhlin, OW;Taghiyev, AF;Cohen, MB
通讯作者：
Cohen, MB
影响因子：
3.6
作者：
Grataroli, R;Vindrieux, D;Benahmed, M
通讯作者：
Benahmed, M
影响因子：
3.5
作者：
Pan, GH;Ni, J;Dixit, VM
通讯作者：
Dixit, VM
人类激动的跟踪受体抗体mapatumumab和lexatumumab诱导恶性间皮瘤中凋亡，并与顺铂协同作用。
影响因子：
37.3
作者：
Belyanskaya, Larisa L.;Marti, Thomas M.;Hopkins-Donaldson, Sally;Kurtz, Stefanie;Felley-Bosco, Emanuela;Stahel, Rolf A.
通讯作者：
Stahel, Rolf A.
DOI：
10.1084/jem.186.7.1165
发表时间：
1997-10-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Degli-Esposti MA;Smolak PJ;Walczak H;Waugh J;Huang CP;DuBose RF;Goodwin RG;Smith CA
通讯作者：
Smith CA