@article{oai:repo.qst.go.jp:00046578,
 author = {Yoshii, Yukie and Furukawa, Takako and Oyama, Nobuyuki and Hasegawa, Yoko and Kiyono, Yashushi and Nishii, Ryuichi and Waki, Atsuo and Tsuji, Atsushi and Sogawa, Chizuru and Wakizaka, Hidekatsu and Fukumura, Toshimitsu and Yoshii, Hiroshi and Fujibayashi, Yasuhisa and Saga, Tsuneo and et.al and 吉井 幸恵 and 古川 高子 and 西井 龍一 and 脇 厚生 and 辻 厚至 and 曽川 千鶴 and 脇坂 秀克 and 福村 利光 and 吉井 裕 and 藤林 康久 and 佐賀 恒夫},
 issue = {5},
 journal = {PLoS ONE (Online only:URL:http://www.plosone.org)},
 month = {May},
 note = {Fatty acid synthase (FASN) expression is elevated in several cancers, and this over-expression is associated with poor prognosis. Inhibitors of FASN, such as orlistat, reportedly show antitumor effects against cancers that over-express FASN, making FASN a promising therapeutic target. However, large variations in FASN expression levels in individual tumors have been observed, and methods to predict FASN-targeted therapy outcome before treatment are required to avoid unnecessary treatment. In addition, how FASN inhibition affects tumor progression remains unclear. Here, we showed the method to predict FASN-targeted therapy outcome using radiolabeled acetate uptake and presented mechanisms of FASN inhibition with human prostate cancer cell lines, to provide the treatment strategy of FASN-targeted therapy. We revealed that tumor uptake of radiolabeled acetate reflected the FASN expression levels and sensitivity to FASN-targeted therapy with orlistat in vitro and in vivo. FASN-targeted therapy was noticeably effective against tumors with high FASN expression, which was indicated by high acetate uptake. To examine mechanisms, we established FASN knockdown prostate cancer cells by transduction of short-hairpin RNA against FASN and investigated the characteristics by analyses on morphology and cell behavior and microarray-based gene expression profiling. FASN inhibition not only suppressed cell proliferation but prevented pseudopodia formation and suppressed cell adhesion, migration, and invasion. FASN inhibition also suppressed genes involved in production of intracellular second messenger arachidonic acid and androgen hormones, both of which promote tumor progression. Collectively, our data demonstrated that uptake of radiolabeled acetate is a useful predictor of FASN-targeted therapy outcome. This suggests that [1-(11)C]acetate positron emission tomography (PET) could be a powerful tool to accomplish personalized FASN-targeted therapy by non-invasive visualization of tumor acetate uptake and selection of responsive tumors. FASN-targeted therapy could be an effective treatment to suppress multiple steps related to tumor progression in prostate cancers selected by [1-(11)C]acetate PET.},
 title = {Fatty Acid synthase is a key target in multiple essential tumor functions of prostate cancer: uptake of radiolabeled acetate as a predictor of the targeted therapy outcome.},
 volume = {8},
 year = {2013}
}