Lee S, Jiang P, Wang W, Feng W, Yu G
Neoplasma. 2014;61(5):546-52. doi: 10.4149/neo_2014_067.
Protease-activated receptors (PARs) are a unique family of G-protein coupled receptors. PAR4, a member of PARs family, was reported to be related to the development of cancers. Whether PAR4 plays a role in the progress of esophageal squamous cancer is unknown. In this study, differential expression of PAR4 in esophageal squamous cancer was measured by real-time PCR (n = 28), western blot and tissue microarrays (n = 78). The results showed that PAR4 expression was remarkably decreased in esophageal squamous cancer tissues compared with the matched noncancerous tissues, especially in low differentiation and positive distant metastasis carcinoma tissues. Furthermore, the methylation level of PAR4 promoter in esophageal cancer cells and normal epithelial cells was determined. Human esophageal cancer cells TE-1 displayed significant hypermethylation of 19 CpG sites, but pronounced hypomethylation of the sites in esophageal epithelial cells HEEpiC. The results suggested that down-regulation expression of PAR4 occurs frequently in esophageal squamous cancers, and the loss of PAR4 expression may partly result from hypermethylation of the PAR4 promoter. That PAR4 expression difference in tumor progression possibly makes PAR4 become a molecular mark of tumor diagnosis.
蛋白酶激活受体（PARs）是一类独特的G蛋白偶联受体家族。PAR4是PARs家族的成员之一，据报道与癌症的发展有关。PAR4在食管鳞状癌进展中是否发挥作用尚不清楚。在本研究中，通过实时PCR（n = 28）、蛋白质印迹法和组织芯片（n = 78）检测了PAR4在食管鳞状癌中的差异表达。结果显示，与配对的非癌组织相比，食管鳞状癌组织中PAR4表达显著降低，尤其是在低分化和远处转移阳性的癌组织中。此外，还测定了食管癌细胞和正常上皮细胞中PAR4启动子的甲基化水平。人食管癌细胞TE-1显示19个CpG位点显著高甲基化，但食管上皮细胞HEEpiC中的这些位点则明显低甲基化。结果表明，PAR4表达下调在食管鳞状癌中频繁发生，PAR4表达缺失可能部分归因于PAR4启动子的高甲基化。PAR4在肿瘤进展中的表达差异可能使PAR4成为肿瘤诊断的分子标志物。
