Urotensin II Receptor Predicts the Clinical Outcome of Prostate Cancer Patients and Is Involved in the Regulation of Motility of Prostate Adenocarcinoma Cells
Urotensin II Receptor Predicts the Clinical Outcome of Prostate Cancer Patients and Is Involved in the Regulation of Motility of Prostate Adenocarcinoma Cells
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DOI：
10.1002/jcb.22933
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发表时间：
2011-01-01
影响因子：
4
通讯作者：
Caraglia, Michele
中科院分区：
文献类型：
--
作者：
Grieco, Paolo;Franco, Renato;Caraglia, Michele
尾加压素II（UT-II）是一种强有力的血管收缩肽，其受体（UTR）与人肾上腺皮质癌的增殖有关。在这项研究中，我们评估了UTR表达和预后的人前列腺癌和参与这种受体在体内和体外模型的生物学特性的调节之间的相关性。UTR mRNA和蛋白质，通过实时PCR和蛋白质印迹法，分别评估，仅在雄激素依赖性LNCaP细胞中以高水平表达。为了研究UTR在人前列腺肿瘤发生中的变化，我们还评估了195个人前列腺组织样本中UTR的体内表达。UTR在增生组织中总是以低强度表达，而在高分化癌中总是以高强度表达（Gleason 2-3）。此外，我们还评估了UTR的拮抗剂urantide对LNCaP细胞迁移和侵袭的影响。Urantide诱导LNCaP细胞的运动性和侵袭性的剂量依赖性降低，其特征性阿米巴样运动似乎有利于其恶性。这些作用通过下调LNCaP细胞上黏着斑激酶的自磷酸化和整合素表面表达而被证实。对细胞运动和侵袭的影响可能是由于urantide和shRNAUTR诱导的RhoA活性抑制。这些数据表明，UTR可以被认为是人类前列腺腺癌患者的预后标志物。J.细胞。112：341-353，2011. (C)2010 Wiley Periodicals，Inc.
Urotensin II (UT-II) is a potent vasoconstrictor peptide and its receptor (UTR) was correlated with human cortico-adrenal carcinoma proliferation. In this study, we have evaluated the correlation between UTR expression and prognosis of human prostate adenocarcinoma and the involvement of this receptor in the regulation of biological properties on both in vivo and in vitro models. UTR mRNA and protein, evaluated by real-time PCR and Western blotting, respectively, were expressed at high levels only in androgen-dependent LNCaP cells. In order to investigate UTR changes occurring in human prostate tumorigenesis, we have also evaluated the expression of UTR in vivo in 195 human prostate tissue samples. UTR was always expressed at low intensity in hyperplastic tissues and at high intensity in well-differentiated carcinomas (Gleason 2-3). Moreover, we have evaluated the effects of an antagonist of UTR, urantide on migration and invasion of LNCaP cells. Urantide induced a dose-dependent decrease of motility and invasion of LNCaP cells whose characteristic ameboid movement seems to be advantageous for their malignancy. These effects were paralleled by down-regulating the autophosphorylation of focal adhesion kinase and the integrin surface expression on LNCaP cells. The effects on cell motility and invasion were likely due to the inhibition of RhoA activity induced by both urantide and shRNA UTR. These data suggest that UTR can be considered a prognostic marker in human prostate adenocarcinoma patients. J. Cell. Biochem. 112: 341-353, 2011. (C) 2010 Wiley Periodicals, Inc.