Different effects of corticotropin-releasing factor and urocortin 2 on apoptosis of prostate cancer cells in vitro
Different effects of corticotropin-releasing factor and urocortin 2 on apoptosis of prostate cancer cells in vitro
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DOI：
10.1530/jme-11-0048
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发表时间：
2011-10-01
影响因子：
3.5
通讯作者：
Li, Shengnan
中科院分区：
文献类型：
--
作者：
Jin, Lai;Zhang, Qichun;Li, Shengnan
尿皮质素（Urocortin，Ucn）是一种促肾上腺皮质激素释放因子（corticotropin-releasing factor，CRF）相关的神经肽，可与CRF 1型受体（CRFR 1）和CRFR 2结合。然而，还没有报道阐明Ucn通过这两种受体在前列腺癌中的作用。本研究检测了CRFR 1和CRFR 2在小鼠前列腺癌细胞系RM-1中的表达，并分别在CRFR 1和CRFR 2选择性激动剂CRF或Ucn 2存在下监测细胞凋亡。CRF促进细胞凋亡，而Ucn 2发挥相反的作用。CRF减少Bcl-2表达，诱导Bax表达，并使线粒体膜电位超极化以激活caspase-9。Ucn 2则相反，上调Bcl-2的表达，下调Bax的表达，其中Akt的磷酸化和环磷酸腺苷反应元件结合（CREB）参与了Ucn 2的作用。在Ucn 2之前用磷脂酰肌醇3激酶/Akt抑制剂（LY-294002）预处理导致CREB磷酸化下调，从而降低Bcl-2表达。CRF和Ucn 2的这些作用分别被CRFR 1和CRFR 2选择性拮抗剂antalarmin（Anta）和antisauvagine-30所消除。在LNCaP细胞系中，观察到CRF和Ucn 2对细胞凋亡的类似作用。总之，我们的研究结果表明CRFR 1和CRFR 2在前列腺癌中的表达，并表明两种不同的CRFR的相反的凋亡作用。这些数据可能有助于揭示内源性Ucn在前列腺肿瘤发生和发展中的病理生理功能。分子内分泌学杂志（2011）47，219-227
Urocortin (Ucn), a corticotropin-releasing factor (CRF)-related neuropeptide binding both CRF type 1 receptor (CRFR1) and CRFR2, has recently been found in prostate cancer. However, no report has yet been known to elucidate the roles of Ucn in prostate cancer via the two receptors. In this study, the expression of both CRFR1 and CRFR2 in the mouse prostate cancer cell line RM-1 were detected and cellular apoptosis was monitored in the presence of CRF or Ucn2, the CRFR1- and CRFR2-selective agonist respectively. CRF promoted apoptosis while Ucn2 exerted the opposite effect. CRF reduced Bcl-2 expression, induced Bax expression, and hyperpolarized the mitochondrial membrane potential to activate caspase-9. On the contrary, Ucn2 increased Bcl-2 expression and decreased Bax expression, in which phosphorylation of Akt and cyclic AMP response element-binding (CREB) was involved. Pretreatment with phosphatidylinositide 3-kinase/Akt inhibitor (LY-294002) prior to Ucn2 led to downregulation of CREB phosphorylation and hence reduced Bcl-2 expression. These effects of CRF and Ucn2 were abolished by antalarmin (Anta) and antisauvagine-30, the CRFR1- and CRFR2-selective antagonist respectively. In LNCaP cell line, similar effects on cell apoptosis by CRF and Ucn2 were observed. In summary, our results demonstrated CRFR1 and CRFR2 expression in prostate cancer and indicated the opposite apoptotic roles of the two different CRFRs. These data may contribute to uncovering the pathophysiological function of endogenous Ucn in prostate tumorigenesis and progression. Journal of Molecular Endocrinology (2011) 47, 219-227