Increased intratumoral androgens in human breast carcinoma following aromatase inhibitor exemestane treatment

Kiyoshi Takagi, Yasuhiro Miki, Shuji Nagasaki, Hisashi Hirakawa, Yoshiaki Onodera, Jun Ichi Akahira, Takanori Ishida, Mika Watanabe, Izo Kimijima, Shin Ichi Hayashi, Hironobu Sasano, Takashi Suzuki

研究成果: Article査読

56 被引用数 (Scopus)

抄録

Sex steroids play important roles in the development of many human breast carcinomas, and aromatase inhibitors are used for the anti-estrogen therapy. Recent studies have demonstrated that aromatase suppressed 5α- dihydrotestosterone (DHT) synthesis in breast carcinoma cells, but intratumoral concentration of androgens and its significance have not been reported in the breast carcinoma patients treated with aromatase inhibitors. Therefore, we examined androgen concentrations in breast carcinoma tissues treated with exemestane, and further performed in vitro studies to characterize the significance of androgen actions. Intratumoral DHT concentration was significantly higher in breast carcinoma tissues following exemestane treatment (n=9) than those without the therapy (n=7), and 17β-hydroxysteroid dehydrogenase type 2 (17βHSD2) status was significantly altered to be positive after the treatment. Following in vitro studies showed that 17βHSD2 expression was dose dependently induced by both DHT and exemestane in T-47D breast carcinoma cells, but these inductions were not additive. DHT-mediated induction of 17βHSD2 expression was markedly suppressed by estradiol (E2) in T-47D cells. E2-mediated cell proliferation was significantly inhibited by DHT in T-47D cells, associated with an increment of 17βHSD2 expression level. These findings suggest that intratumoral androgen actions are increased during exemestane treatment. 17βHSD2 is a potent DHT-induced gene in human breast carcinoma, and may not only be involved in anti-proliferative effects of DHT on breast carcinoma cells but also serve as a potential marker for response to aromatase inhibitor in the breast carcinoma patients.

本文言語English
ページ(範囲)415-430
ページ数16
ジャーナルEndocrine-Related Cancer
17
2
DOI
出版ステータスPublished - 2010 6

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 腫瘍学
  • 内分泌学
  • 癌研究

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