[Frontiers in Bioscience 14, 2285-2292, January 1, 2009]

Expression of aromatase CYP19 and its relationship with parameters in NSCLC

Tsunehiro Oyama1,2Norio Kagawa3, Kenji Sugio1, Hidetaka Uramoto1, Osamu Hatano4, Nobuhiro Harada5, Kazuhiro Kaneko6, Toshihiro Kawamoto2, Kosei Yasumoto1

1Second Department of Surgery, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan, 2Department of Environmental Health, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan, 3Department of Biochemistry, Saarland University, D 66041 Saarbrucken, Germany, 4Department of Anatomy, Nara Medical University, School of Medicine, Nara, 634-8521, Japan, 5Department of Biochemistry, Fujita Health University School of Medicine, Toyoake 470-1192, Japan, 6Division of Digestive Endoscopy/Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, 277-8577, Japan

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods
3.1. Preparation of the human aromatase and anti-bodies
3.2. NSCLC specimens
3.3. Immunohistochemical staining
4. Results
4.1. Expression, purification of human aromatase, and preparation of polyclonal antibodies
4.2. Expression of CYP19 in NSCLC
4.3. Correlation among CYP19 and the other CYP for the expression in NSCLC
4.4. Mutations in p53 and the frequency of CYP19 expression
5. Discussion
6. Acknowledgements
7. References

1. ABSTRACT

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.