Changes in aromatase (CYP19) gene promoter usage in non-small cell lung cancer

フォーマット:

論文

責任表示:

Demura, Masashi ; Demura, Yoshiki ; Ameshima, Shingo ; Ishizaki, Takeshi ; Sasaki, Masato ; Miyamori, Isamu ; Yamagishi, Masakazu ; Takeda, Yoshiyu ; Bulun, Serdar E.

言語:

英語

出版情報:

Elsevier, 2011-09-01

著者名:

Demura, Masashi

Demura, Yoshiki

Ameshima, Shingo

Ishizaki, Takeshi

Sasaki, Masato

Miyamori, Isamu

Yamagishi, Masakazu

Takeda, Yoshiyu

Bulun, Serdar E.

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掲載情報:

Lung Cancer

ISSN:

0169-5002      

巻:

73

通号:

3

開始ページ:

289

終了ページ:

293

バージョン:

author

概要:

金沢大学医薬保健研究域医学系<br />In humans, aromatase (CYP19) gene expression is regulated via alternative promoters. Activation of each promoter gives rise to a CYP19 mRNA species with a unique 5′-untranslated region. Inhibition of aromatas … e has been reported to downregulate lung tumor growth. The genetic basis for CYP19 gene expression and aromatase activity in lung cancer remains poorly understood. We analyzed tissues from 15 patients with non-small cell lung cancer (NSCLC) to evaluate CYP19 promoter usage and promoter-specific aromatase mRNA levels in NSCLC tumor tissues and adjacent non-malignant tissues. CYP19 promoter usage was determined by multiplex RT-PCR and aromatase mRNA levels were measured with real-time RT-PCR. In non-malignant tissues, aromatase mRNA was primarily derived from activation of CYP19 promoter I.4. Although promoter I.4 usage was also dominant in tumor tissues, I.4 activation was significantly lower compared with adjacent non-malignant tissues. Activity of promoters I.3, I.1 and I.7 was significantly higher in tumor tissues compared with non-malignant tissues. In 4 of 15 cases of non-small cell lung cancer, switching from CYP19 promoter I.4 to the alternative promoters II, I.1 or I.7 was observed. In 9 cases, there were significantly higher levels of aromatase mRNA in lung tumor tissues compared with adjacent non-malignant tissues. These findings suggest aberrant activation of alternative CYP19 promoters that may lead to upregulation of local aromatase expression in some cases of NSCLC. Further studies are needed to examine the impact of alternative CYP19 promoter usage on local estrogen levels and lung tumor growth. © 2011 Elsevier Ireland Ltd. All rights reserved. 続きを見る

URL:

http://hdl.handle.net/2297/27075