Kaushal Varsha, Kohli Manish, Dennis Richard A, Siegel Eric R, Chiles Walter W, Mukunyadzi Perkins
Department of Internal Medicine, University of Arkansas for Medical Sciences, and Division of Hematology/Oncology, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas 72205, USA.
Prostate. 2006 Feb 15;66(3):273-82. doi: 10.1002/pros.20326.
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 PAR1 expression in prostate cancer.
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.
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=5.89x10(-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 PAR1 correlated statistically significantly with advanced disease stage (P=0.0006) and pre-operative PSA levels (P=0.005) in these samples.
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.
蛋白酶激活受体（PARs）的异常表达与多种癌症的血管生成增加、肿瘤生长和转移有关。我们评估了PAR1在前列腺癌中的表达状况。
本研究使用实时逆转录聚合酶链反应和免疫印迹法，比较了新鲜切除的早期局限性疾病（n = 9）至晚期转移性疾病患者（n = 7）的前列腺组织中PAR1 RNA和蛋白质的丰度水平。使用免疫组织化学染色对前列腺增生（n = 27）、早期（n = 32）和晚期（n = 22）前列腺癌的前列腺标本进行PAR1表达和定位评估。还进行了PAR1表达与血管内皮生长因子（VEGF）家族生长因子及其受体表达以及患者临床病理特征的关联分析。
与早期前列腺癌相比，晚期前列腺癌中PAR1 RNA表达高2.39倍（P = 0.024），其蛋白质表达高2.75倍（P = 5.89×10⁻⁵）。PAR1表达定位于前列腺肿瘤区域血管网络中的内皮细胞。在这些样本中，PAR1表达与疾病晚期（P = 0.0006）和术前前列腺特异抗原（PSA）水平（P = 0.005）具有统计学显著相关性。
这些发现表明PAR1在前列腺癌中表达增加。其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。
