Oyama Tsunehiro, Kagawa Norio, Sugio Kenji, Uramoto Hidetaka, Hatano Osamu, Harada Nobuhiro, Kaneko Kazuhiro, Kawamoto Toshihiro, Yasumoto Kosei
Second Department of Surgery and Department of Environmental Health, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
Front Biosci (Landmark Ed). 2009 Jan 1;14(6):2285-92. doi: 10.2741/3379.
Human aromatase (CYP19) responsible for the conversion of androgens to estrogens is expressed not only in gonads and adrenals but also in many other tissues, including normal lungs and lung cancers. To investigate the involvement of CYP19 in lung cancer development, purified CYP19 protein and antibody are required. In this study, we have developed an efficient expression method of human aromatase in E. coli (>1000 nmol/L culture). The protein purified from E. coli was used to raise an antibody against the human CYP19 in rabbits. The resulting antibody showed a high titer judged by ELISA, which allowed us to determine the expression of CYP19 in non-small cell lung cancer (NSCLC). Of 78 NSCLC specimens from Japanese patients, 50 (64%) NSCLC aberrantly expressed CYP19. This CYP19 expression in NSCLC was independent of any clinical and pathological parameters as well as the expression of other P450s, except tumor stage. The results suggest that the aromatase inhibitors might be useful for the management of non-small cell lung cancer in postmenopausal women.
负责将雄激素转化为雌激素的人芳香化酶(CYP19)不仅在性腺和肾上腺中表达,还在许多其他组织中表达,包括正常肺组织和肺癌组织。为了研究CYP19在肺癌发生中的作用,需要纯化的CYP19蛋白和抗体。在本研究中,我们开发了一种在大肠杆菌中高效表达人芳香化酶的方法(培养物中>1000 nmol/L)。从大肠杆菌中纯化的蛋白用于在兔体内制备抗人CYP19的抗体。通过ELISA判断,所得抗体显示出高滴度,这使我们能够确定CYP19在非小细胞肺癌(NSCLC)中的表达。在来自日本患者的78例NSCLC标本中,50例(64%)NSCLC异常表达CYP19。NSCLC中的这种CYP19表达与任何临床和病理参数以及其他P450的表达无关,但肿瘤分期除外。结果表明,芳香化酶抑制剂可能对绝经后女性非小细胞肺癌的治疗有用。