Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa, Japan.
Cancer Sci. 2010 Apr;101(4):1024-8. doi: 10.1111/j.1349-7006.2009.01482.x. Epub 2010 Feb 22.
Human CYP2A13, which is expressed in the respiratory tract, is the most efficient enzyme for the metabolic activation of tobacco-specific nitrosamines such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The relevance of CYP2A13 in carcinogenicity and toxicity in the respiratory tract has been suggested, but the expression of CYP2A13 protein in lung cancer tissues remains to be determined. We first prepared a mouse monoclonal antibody against human CYP2A13. The antibody showed no cross reactivity with the other CYP isoforms including CYP2A6. Using the specific antibody, we performed immunohistochemical analysis for human lung carcinomas. In adenocarcinomas (n = 15), all specimens were positive for the staining and five samples showed strong staining. In squamous cell carcinomas (n = 15) and large cell carcinomas (n = 15), each 14 samples were positive for the staining and two and three samples showed strong staining, respectively. In small cell carcinoma samples (n = 15), eight samples were negative for the staining and five samples showed weak or moderate staining. In conclusion, we first found that the expression of CYP2A13 was markedly increased in non-small cell lung carcinomas. The high expression might be associated with the tumor development and progression in non-small cell lung carcinomas.
人类 CYP2A13 主要在呼吸道中表达,是对烟草特异性亚硝胺(如 4-(甲基亚硝氨基)-1-(3-吡啶基)-1-丁酮(NNK))进行代谢激活的最有效酶。已经提出 CYP2A13 在呼吸道致癌性和毒性中的相关性,但肺癌组织中 CYP2A13 蛋白的表达仍有待确定。我们首先制备了针对人 CYP2A13 的小鼠单克隆抗体。该抗体与其他 CYP 同工酶(包括 CYP2A6)没有交叉反应性。使用特异性抗体,我们对人肺癌进行了免疫组织化学分析。在腺癌(n=15)中,所有标本的染色均为阳性,5 个标本显示强染色。在鳞状细胞癌(n=15)和大细胞癌(n=15)中,每个标本均有 14 个为阳性,分别有 2 个和 3 个标本显示强染色。在小细胞癌标本(n=15)中,有 8 个标本为阴性,有 5 个标本显示弱阳性或中度染色。总之,我们首次发现 CYP2A13 在非小细胞肺癌中的表达明显增加。高表达可能与非小细胞肺癌的肿瘤发生和进展有关。