Changes in Caveolae,Caveolin, and Polymerase 1 and Transcript Release Factor (PTRF) Expression in Prostate Cancer Progression
Changes in Caveolae,Caveolin, and Polymerase 1 and Transcript Release Factor (PTRF) Expression in Prostate Cancer Progression
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DOI：
10.1002/pros.21195
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发表时间：
2010-11-01
期刊：
影响因子：
2.8
通讯作者：
Nicholson, H. D.
中科院分区：
文献类型：
--
作者：
Gould, M. L.;Williams, G.;Nicholson, H. D.
背景小窝是细胞膜上的一种特殊的内陷，参与细胞转运和信号转导的调节。本研究旨在探讨前列腺癌组织中小窝的数量、小窝相关蛋白小窝蛋白-1和小窝蛋白-2、聚合酶1和转录释放因子（PTRF）的表达与前列腺癌的发生、发展的关系。透射电子显微镜被用来调查在正常人前列腺基质，上皮细胞，雄激素依赖性（LNCaP）和雄激素非依赖性（PC 3）癌细胞系的小窝的数量。手术组织获自良性前列腺增生（BPH）、高分化和低分化前列腺癌患者。小窝蛋白-1，小窝蛋白-2，和PTRF表达的组织样本中通过免疫组化和定量Western印迹分析细胞系。在正常前列腺上皮细胞和间质细胞中发现了小窝。LNCaP和PC 3细胞的小窝数量明显减少（P < 0.0001）。PTRF定位于BPH患者组织中的间质细胞和上皮细胞以及体外正常间质细胞和上皮细胞。PTRF表达在LNCaP和PC 3细胞以及癌组织中显著降低。在前列腺组织中，小窝蛋白-1和-2的表达似乎在前列腺癌中增加。与正常上皮细胞相比，LNCaP细胞中Caveolin-1和Caveolin-2的表达降低，而PC 3细胞中Caveolin-2的表达显著升高。这项研究表明，在细胞膜的变化，涉及的小窝和PTRF表达的损失发生与前列腺癌的发展。这些变化伴随着窖蛋白-2的上调。前列腺70：1609-1621，2010。(C)2010 Wiley-Liss，Inc.
BACKGROUND. Caveolae are specialized invaginations in the cell membrane involved in the regulation of cell transport and signal transduction. The aims of this study were to investigate the number of caveolae and expression of caveolae-associated proteins, caveolin-1 and -2, and polymerase 1 and transcript release factor (PTRF) with development of prostate cancer.METHODS. Transmission electron microscopy was used to investigate the number of caveolae in normal human prostate stromal, epithelial cells, and androgen-dependent (LNCaP) and androgen-independent (PC3) cancer cell lines. Surgical tissue was obtained from patients with benign prostatic hyperplasia (BPH), well-differentiated and poorly differentiated prostate cancer. Caveolin-1, caveolin-2, and PTRF expression was identified by immunohistochemistry in tissue samples and quantified by Western blot analysis in cell lines.RESULTS. Caveolae were identified in normal epithelial and stromal prostate cells. The number of caveolae was significantly reduced in LNCaP and PC3 cells (P < 0.0001). PTRF was localized to stromal and epithelial cells in tissue from patients with BPH and in normal stromal and epithelial cells in vitro. PTRF expression was significantly decreased in LNCaP and PC3 cells and also in cancer tissue. In prostate tissue, caveolin-1 and -2 expression appeared to increase in prostate cancer. Caveolin-1 and -2 expression was decreased in LNCaP cells but caveolin-2 expression was significantly increased in PC3 cells compared to normal epithelial cells.CONCLUSIONS. This study demonstrates that changes in the cell membrane involving loss of caveolae and PTRF expression occur with the development of prostate cancer. These changes are accompanied by an up-regulation of caveolin-2. Prostate 70: 1609-1621, 2010. (C) 2010 Wiley-Liss, Inc.