Thrombin receptor expression is upregulated in prostate cancer
Thrombin receptor expression is upregulated in prostate cancer
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DOI：
10.1002/pros.20326
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发表时间：
2006-02-15
期刊：
影响因子：
2.8
通讯作者：
Mukunyadzi, P
中科院分区：
文献类型：
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作者：
Kaushal, V;Kohli, M;Mukunyadzi, P
背景蛋白酶激活受体（PAR）的异常表达与多种癌症的血管生成、肿瘤生长和转移有关。我们评估了PARI在前列腺癌中的表达状态。该研究使用实时逆转录酶聚合酶链反应和免疫印迹法比较了来自早期局限性疾病（n = 9）和晚期转移性疾病患者（n = 7）的新鲜切除的前列腺组织中PAR 1 RNA和蛋白质的丰度水平。PAR 1的表达和定位使用免疫组化染色的前列腺标本与良性前列腺增生（n = 27），早期（n = 32）和晚期（n = 22）前列腺癌进行了评估。还进行了PAR 1表达与VEGF家族生长因子及其受体表达和患者临床病理特征的相关性分析。与早期前列腺癌相比，晚期前列腺癌中PAR 1 RNA表达高2.39倍（P = 0.024），其蛋白表达高2.75倍（P = 5.89 x 10（-5））。PAR 1表达定位于前列腺肿瘤区域血管网的内皮细胞。PARI的表达与这些样本中的晚期疾病分期（P = 0.0006）和术前PSA水平（P = 0.005）具有统计学显著相关性。这些发现表明PAR 1表达在前列腺癌中增加。它在血管网络中的主要表达表明它可能在血管生成中起直接和关键的作用，并且可能是控制或预防疾病进展的治疗干预的相关靶点。
BACKGROUND. Aberrant expression of protease-activated receptors (PARs) has been associated with increased angiogenesis, tumor growth, and metastasis of various cancers. We assessed the status of PARI expression in prostate cancer.METHODS. The study compared the abundance levels of PAR1 RNA and protein using real-time reverse-transcriptase polymerase chain reaction and immunoblotting in freshly resected prostate tissues from early localized-stage disease (n = 9) to those from patients with advanced metastatic disease (n = 7). PAR1 expression and localization was evaluated using immunohistochemical staining of prostate specimens with benign prostatic hyperplasia (n = 27), early(n = 32) and advanced-stage (n = 22) prostate cancer. Association analyses of PAR1 expression with expression of VEGF-family of growth factors, their receptors, and clinicopathological characteristics of the patients were also performed.RESULTS. PAR1 RNA expression in advanced-stage prostate was 2.39-fold higher (P = 0.024) and its protein expression was 2.75-fold higher (P = 5.89 x 10(-5)) when compared with early-stage prostate cancer. PAR1 expression was localized to endothelial cells in vascular network of prostate tumor areas. The expression of PARI correlated statistically significantly with advanced disease stage (P = 0.0006) and pre-operative PSA levels (P = 0.005) in these samples.CONCLUSIONS. These findings demonstrate that PAR1 expression is increased in prostate cancer. Its predominant expression in vascular network suggests that it may play a direct and crucial role in angiogenesis and could be a relevant target for therapeutic interventions to control or to prevent disease progression.