Mauro Annamaria, Lipari Luana, Leone Angelo, Tortorici Silvia, Burruano Francesco, Provenzano Salvatore, Gerbino Aldo, Buscemi Maria
BioNec, Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Facoltŕ di Medicina e Chirurgia, Universitŕ di Palermo, Palermo, Italy.
Folia Histochem Cytobiol. 2010 Dec;48(4):555-63. doi: 10.2478/v10042-010-0066-3.
Cyclooxigenase (COX) is the rate-limiting enzyme for the conversion of arachidonic acid (AA) to prostaglandins (PGs). Two isoforms of COX have been identified: COX-1 is constitutively expressed in many cells and is involved in cell homeostasis, angiogenesis and cell-cell signalling; COX-2 is not expressed in normal condition however it is strongly expressed in inflammation. The oral cavity is constantly exposed to physical and chemical trauma that could lead to mucosal reactions such as hyperplasia, dysplasia and cancer. Early diagnosis is the most important issue to address for a positive outcome of oral cancer; therefore it would be useful to identify molecular markers whose expression is associated with the various stages of oral cancer progression. Since COX enzyme has been involved, with different mechanisms, in the development and progression of malignancies we decided to investigate the expression and localization of COX-1 and COX-2 in normal human oral mucosa and three different pathologies (hyperplasia, dysplasia and carcinoma) by immunohistochemistry and RT-PCR. COX-1 mRNA and protein have been detected already in normal oral mucosa and their expression progressively increases from normal samples towards hyperplasia, dysplasia and finally carcinoma. On the contrary, COX-2 is not expressed in the normal tissue, starts to be expressed in hyperplasia, reaches the maximum activation in dysplasia and then starts to be downregulated in carcinoma.
环氧化酶(COX)是花生四烯酸(AA)转化为前列腺素(PGs)的限速酶。已鉴定出COX的两种同工型:COX-1在许多细胞中组成性表达,参与细胞稳态、血管生成和细胞间信号传导;COX-2在正常情况下不表达,但在炎症中强烈表达。口腔经常受到物理和化学创伤,这可能导致黏膜反应,如增生、发育异常和癌症。早期诊断是口腔癌取得积极治疗结果的最重要问题;因此,识别其表达与口腔癌进展各阶段相关的分子标志物将是有用的。由于COX酶已通过不同机制参与恶性肿瘤的发生和发展,我们决定通过免疫组织化学和逆转录-聚合酶链反应(RT-PCR)研究COX-1和COX-2在正常人口腔黏膜以及三种不同病理状态(增生、发育异常和癌)中的表达和定位。在正常口腔黏膜中已检测到COX-1的信使核糖核酸(mRNA)和蛋白质,其表达从正常样本到增生、发育异常,最终到癌逐渐增加。相反,COX-2在正常组织中不表达,在增生中开始表达,在发育异常中达到最大激活,然后在癌中开始下调。