Physiology and Biophysics Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
Pathological Anatomy Service, Clinic Hospital, University of Chile, Santiago, Chile.
Int J Oncol. 2014 Mar;44(3):647-54. doi: 10.3892/ijo.2014.2254. Epub 2014 Jan 10.
Prostate cancer (PC) is a leading male oncologic malignancy wideworld. During malignant transformation, normal epithelial cells undergo genetic and morphological changes known as epithelial-mesenchymal transition (EMT). Several regulatory genes and specific marker proteins are involved in PC EMT. Recently, syndecans have been associated with malignancy grade and Gleason score in PC. Considering that SNAIL is mainly a gene repressor increased in PC and that syndecan promoters have putative binding sites for this repressor, we propose that SNAIL might regulate syndecan expression during PC EMT. The aim of this study was to analyze immunochemically the expression of SNAIL, syndecans 1 and 2 and other EMT markers in a tissue microarray (TMA) of PC samples and PC cell lines. The TMAs included PC samples of different Gleason grade and benign prostatic hyperplasia (BPH) samples, as non‑malignant controls. PC3 and LNCaP cell lines were used as models of PC representing different tumorigenic capacities. Semi-quantitative immunohistochemistry was performed on TMAs and fluorescence immunocytochemistry and western blot analysis were conducted on cell cultures. Results show that SNAIL exhibits increased expression in high Gleason specimens compared to low histological grade and BPH samples. Accordingly, PC3 cells show higher SNAIL expression levels compared to LNCaP cells. Conversely, syndecan 1, similarly to E-cadherin (a known marker of EMT), shows a decreased expression in high Gleason grades samples and PC3 cells. Interestingly, syndecan 2 shows no changes associated to histological grade. It is concluded that increased SNAIL levels in advanced PC are associated with low expression of syndecan 1. The mechanism by which SNAIL regulates the expression of syndecan 1 remains to be investigated.
前列腺癌 (PC) 是全球男性主要的恶性肿瘤之一。在恶性转化过程中,正常上皮细胞发生遗传和形态变化,称为上皮-间充质转化 (EMT)。几个调节基因和特定的标记蛋白参与了 PC EMT。最近,连接蛋白与 PC 的恶性程度和 Gleason 评分相关。考虑到 SNAIL 主要是 PC 中上调的基因抑制剂,并且连接蛋白启动子具有该抑制剂的潜在结合位点,我们提出 SNAIL 可能在 PC EMT 期间调节连接蛋白的表达。本研究的目的是分析 SNAIL、连接蛋白 1 和 2 以及其他 EMT 标志物在 PC 样本和 PC 细胞系的组织微阵列 (TMA)中的免疫化学表达。TMA 包括不同 Gleason 分级的 PC 样本和良性前列腺增生 (BPH) 样本作为非恶性对照。PC3 和 LNCaP 细胞系被用作代表不同致瘤能力的 PC 模型。对 TMA 进行半定量免疫组织化学染色,对细胞培养物进行荧光免疫细胞化学和 Western blot 分析。结果表明,与低组织学分级和 BPH 样本相比,SNAIL 在高 Gleason 标本中表达增加。相应地,PC3 细胞比 LNCaP 细胞表现出更高的 SNAIL 表达水平。相反,连接蛋白 1 与 E-钙黏蛋白 (EMT 的已知标志物) 一样,在高 Gleason 分级样本和 PC3 细胞中表达降低。有趣的是,连接蛋白 2 的表达与组织学分级无关。结论是,晚期 PC 中 SNAIL 水平的升高与连接蛋白 1 的低表达相关。SNAIL 调节连接蛋白 1 表达的机制仍有待研究。