高脂肪食による前立腺癌の進展促進の分子メカニズムの解明

2009 年度 研究成果報告書

• 研究課題/領域番号: 19390411
• 研究種目: 基盤研究(B)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 泌尿器科学
• 研究機関: 秋田大学
• 研究代表者: 羽渕 友則 秋田大学, 大学院・医学系研究科, 教授 (00293861)
• 研究分担者: 鈴木 聡 九州大学, 生体防御研究所, 教授 (10311565) ; 中村 彰 秋田大学, 大学院・医学系研究科, 教授 (20155815) ; 大山 力 弘前大学, 大学院・医学系研究科, 教授 (80282135) ; 土谷 順彦 秋田大学, 大学院・医学系研究科, 准教授 (70282176) ; 湯浅 健 財団法人癌研究会, 附属病院化学療法科, 医長 (00314162)
• 研究期間 (年度): 2007 – 2009
• キーワード: 前立腺癌 / 高脂肪食 / マイクロアレイ / 発現解析 / IGF-1 / LNCaP / Fn-14 / TWEAK

研究概要

目的は高脂肪食と前立腺癌の関係を分子レベルで解明し、その克服の分子標的を見出し、治療や予防戦略に繋がる知見を得ることである。結果として、前立腺細胞株のマウス異種移植腫瘍のサイズが高脂肪食により増大することを確認し、網羅的mRNA発現解析により標的候補遺伝子を同定した。標的分子経路の候補としてTWEAK-Fn14シグナル伝達経路を解析し、このシグナルが内分泌療法不応性前立腺癌の浸潤能や進展に関与していることを示した。

研究成果

• [雑誌論文] Relationship Between Bone Mineral Density and Androgen-deprivation Therapy in Japanese Prostate Cancer Patients (2010)
  • 著者名/発表者名: Yuasa T, Maita S, Tsuchiya N, Ma Z, Narita S, Horikawa Y, Yamamoto S, Yonese J, Fukui I, Takahashi S, Hatake K, Habuchi T.
  • 雑誌名: Urology
• [雑誌論文] Cystoprostatectomy as a treatment of prostate cancer involving the bladder neck (2009)
  • 著者名/発表者名: Kumazawa T, Tsuchiya N, Saito M, Inoue T, Narita S, Horikawa Y, Yuasa T, Satoh S, Kato T, Nanjyo H, Habuchi T.
  • 雑誌名: Urol Int. 83(2) ページ: 141-5
• [雑誌論文] Clinical significance of a single nucleotide polymorphism and allelic imbalance of matrix metalloproteinase-1 promoter region in prostate cancer (2009)
  • 著者名/発表者名: Tsuchiya N, Narita S, Kumazawa T, Inoue T, Ma Z, Tsuruta H, Saito M, Horikawa Y, Yuasa T, Satoh S, Ogawa O, Habuchi T.
  • 雑誌名: Oncol Rep. 22(3) ページ: 493-9
• [雑誌論文] The novel tumor-suppressor Mel-18 in prostate cancer : Its functional polymorphism, expression, and clinical significance (2009)
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  • 雑誌名: Int J Cancer 125(12) ページ: 2836-43
• [雑誌論文] Prevalence of skeletal complications and their impact on survival of hormone refractory prostate cancer patients in Japan (2009)
  • 著者名/発表者名: Inoue T, Segawa T, Kamba T, Yoshimura K, Nakamura E, Nishiyama H, Ito N, Kamoto T, Habuchi T, Ogawa O.
  • 雑誌名: Urology 73(5) ページ: 1104-9
• [雑誌論文] Intravesical administration of gammadelta T cells successfully prevents the growth of bladder cancer in the murine model (2009)
  • 著者名/発表者名: Yuasa T, Sato K, Ashihara E, Takeuchi M, Maita S, Tsuchiya N, Habuchi T, Maekawa T, Kimura S.
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• [雑誌論文] Identification of mRNA splicing factors as the endothelial receptor for carbohydrate-dependent lung colonization of cancer cells (2009)
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  • 雑誌名: Proc Natl Acad Sci USA 106(9) ページ: 3095-100
• [雑誌論文] (2009)
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• [雑誌論文] Core3 O-glycan synthase suppresses tumor formation and metastasis of prostate carcinoma PC3 and LNCaP cells through down-regulation of alpha2beta1 integrin complex (2009)
  • 著者名/発表者名: Lee SH, Hatakeyama S, Yu SY, Bao X, Ohyama C, Khoo KH, Fukuda MN, Fukuda M.
  • 雑誌名: J Biol Chem. 284(25) ページ: 17157-69
• [雑誌論文] Single nucleotide polymorphisms of microRNA machinery genes modify the risk of renal cell carcinoma (2008)
  • 著者名/発表者名: Horikawa Y, Wood CG, Yang H, Zhao H, Ye Y, Gu J, Lin J, Habuchi T, Wu X.
  • 雑誌名: Clin Cancer Res. 14(23) ページ: 7956-62
• [雑誌論文] Characterization of prostate cancer detected at repeat biopsy (2008)
  • 著者名/発表者名: Yuasa T, Tsuchiya N, Kumazawa T, Inoue T, Narita S, Saito M, Horikawa Y, Satoh S, Habuchi T.
  • 雑誌名: BMC Urol. 8(1) ページ: 14
• [雑誌論文] Polymorphisms of fibroblast growth factor receptor 4 have association with the development of prostate cancer and benign prostatic hyperplasia and the progression of prostate cancer in a Japanese population (2008)
  • 著者名/発表者名: Ma Z, Tsuchiya N, Yuasa T, Inoue T, Kumazawa T, Narita S, Horikawa Y, Tsuruta H, Obara T, Saito M, Satoh S, Ogawa O, Habuchi T.
  • 雑誌名: Int J Cancer 123(11) ページ: 2574-2579
• [雑誌論文] Pten deficiency in melanocytes results in resistance to hair graying and susceptibility to carcinogen-induced melanomagenesis (2008)
  • 著者名/発表者名: Inoue-Narita T, Hamada K, Sasaki T, Hatakeyama S, Fujita S, Kawahara K, Sasaki M, Kishimoto H, Eguchi S, Kojima I, Beermann F, Kimura T, Osawa M, Itami S, Mak TW, Nakano T, Manabe M, Suzuki A.
  • 雑誌名: Cancer Res. 68(14) ページ: 5760-8
• [雑誌論文] Bone mineral density in Japanese prostate cancer patients under androgen-deprivation therapy (2008)
  • 著者名/発表者名: Wang W, Yuasa T, Tsuchiya N, Maita S, Kumazawa T, Inoue T, Saito M, Ma Z, Obara T, Tsuruta H, Satoh S, Habuchi T.
  • 雑誌名: Endocr Relat Cancer 15(4) ページ: 943-52
• [雑誌論文] Association of genetic polymorphisms at 8q24 with the risk of prostate cancer in a Japanese population (2008)
  • 著者名/発表者名: Terada N, Tsuchiya N, Ma Z, Shimizu Y, Kobayashi T, Nakamura E, Kamoto T, Habuchi T, Ogawa O.
  • 雑誌名: Prostate 68(15) ページ: 1689-95
• [雑誌論文] Normal development is an integral part of tumorigenesis in T cell-specific PTEN-deficient mice (2008)
  • 著者名/発表者名: Xue L, Nolla H, Suzuki A, Mak TW, Winoto A.
  • 雑誌名: Proc Natl Acad Sci USA 105(6) ページ: 2022-7
• [雑誌論文] The roles of PTEN in development, physiology and tumorigenesis in mouse models : a tissue-by-tissue survey (2008)
  • 著者名/発表者名: Knobbe CB, Lapin V, Suzuki A, Mak TW
  • 雑誌名: Oncogene 27(41) ページ: 5398-415
• [雑誌論文] Drug related genetic polymorphisms affecting adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin in patients with urothelial cancer (2008)
  • 著者名/発表者名: Tsuchiya N, Inoue T, Narita S, Kumazawa T, Saito M, Obara T, Tsuruta H, Horikawa Y, Yuasa T, Satoh S, Habuchi T.
  • 雑誌名: J Urol. 180(6) ページ: 2389-95
• [雑誌論文] A genetic polymorphism of the osteoprotegerin gene is associated with an increased risk of advanced prostate cancer (2008)
  • 著者名/発表者名: Narita N, Yuasa T, Tsuchiya N, Kumazawa T, Narita S, Inoue T, Ma Z, Saito M, Horikawa Y, Satoh S, Ogawa O, Habuchi T.
  • 雑誌名: BMC Cancer 8 ページ: 224
• [雑誌論文] Clinical implications of the MDM2 SNP309 and p53 Arg72Pro polymorphisms in transitional cell carcinoma of the bladder (2008)
  • 著者名/発表者名: Horikawa Y, Nadaoka J, Saito M, Kumazawa T, Inoue T, Yuasa T, Tsuchiya N, Nishiyama H, Ogawa O, Habuchi T.
  • 雑誌名: Oncol Rep. 20(1) ページ: 49-55
• [雑誌論文] BPDE Induced Lymphocytic Chromosome 3p Deletions May Predict Renal Cell Carcinoma Risk (2008)
  • 著者名/発表者名: Zhu Y, Horikawa Y, Yang H, Wood CG, Habuchi T, Wu X.
  • 雑誌名: J Urol. 179(6) ページ: 2416-21
• [雑誌論文] Prospective Evaluation of Selection Criteria for Active Surveillance in Japanese Patients with Stage T1cN0M0 Prostate Cancer (2008)
  • 著者名/発表者名: Kakehi Y, Kamoto T, Shiraishi T, Ogawa O, Suzukamo Y, Fukuhara S, Saito Y, Tobisu KI, Kakizoe T, Shibata T, Fukuda H, Akakura K, Suzuki H, Shinohara N, Egawa S, Irie A, Sato T, Maeda O, Meguro N, Sumiyoshi Y, Suzuki T, Shimizu N, Arai Y, Terai A, Kato T, Habuchi T, Fujimoto H, Niwakawa M.
  • 雑誌名: Jpn J Clin Oncol 38(2) ページ: 122-8
• [雑誌論文] Candidate genes involved in enhanced growth of human prostate cancer under high fat feeding identified by microarray analysis (2008)
  • 著者名/発表者名: Narita S, Tsuchiya N, Saito M, Inoue T, Kumazawa T, Yuasa T, Nakamura A, Habuchi T.
  • 雑誌名: Prostate 68(3) ページ: 321-35
• [雑誌論文] Prognostic significance of HIF-1alpha polymorphisms in transitional cell carcinoma of the bladder (2008)
  • 著者名/発表者名: Nadaoka J, Horikawa Y, Saito S, Kumazawa T, Inoue T, Narita S, Yuasa T, Satoh S, Nishiyama H, Ogawa O, Tsuchiya N, Habuchi T.
  • 雑誌名: Int J Cancer 122(6) ページ: 1297-302
• [雑誌論文] Possible survival benefit of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin combination therapy (HD-MVAC) over conventional MVAC in metastatic urothelial carcinoma patients (2007)
  • 著者名/発表者名: Inoue T, Obara T, Saito M, Kumazawa T, Yuasa T, Matuura S, Tsuchiya N, Satoh S, Habuchi T.
  • 雑誌名: Hinyokika Kiyo. 53(9) ページ: 613-8
• [雑誌論文] Clinical implication of vascular endothelial growth factor T-460C polymorphism in the risk and progression of prostate cancer (2007)
  • 著者名/発表者名: Fukuda H, Tsuchiya N, Narita S, Kumazawa T, Horikawa Y, Inoue T, Saito M, Yuasa T, Matsuura S, Satoh S, Ogawa O, Habuchi T.
  • 雑誌名: Oncol Rep. 18(5) ページ: 1155-63
• [雑誌論文] Zoledronic acid-a multiplicity of anti-cancer action (2007)
  • 著者名/発表者名: Yuasa T, Kimura S, Ashihara E, Habuchi T, Maekawa T.
  • 雑誌名: Curr Med Chem. 14(20) ページ: 2126-35
• [雑誌論文] Lymphatic invasion is a prognostic factor for bladder cancer treated with radical cystectomy (2007)
  • 著者名/発表者名: Horikawa Y, Kumazawa T, Narita S, Inoue T, Yuasa T, Matsuura S, Nanjo H, Satoh S, Tsuchiya N, Habuchi T.
  • 雑誌名: Int J Clin Oncol. 12(2) ページ: 131-6
• [雑誌論文] Low concentrations of the histone deacetylase inhibitor, depsipeptide, enhance the effects of gemcitabine and docetaxel in hormone refractory prostate cancer cells (2007)
  • 著者名/発表者名: Kanzaki M, Kakinuma H, Kumazawa T, Inoue T, Saito M, Narita S, Yuasa T, Tsuchiya N, Habuchi T.
  • 雑誌名: Oncol Rep. 17(4) ページ: 761-7
• [学会発表] Evaluation of outcomes and genetic predictive factors for prognosis and toxicity in hormone-refractory prostate cancer patients following combination therapy with docetaxel, estramustine, and carboplatin (2009)
  • 著者名/発表者名: Narita S., et al.
  • 学会等名: The 103rd Annual Meeting of the American Urological Association
  • 発表場所: Chicago, USA
  • 年月日: 20090400
• [学会発表] Overexpression of BCL-2 seen in resifual prostate cancer after neoadjuvant chemohormonal therapy with docetaxel for locally advanced prostate cancer (2009)
  • 著者名/発表者名: Kumazawa T., et al.
  • 学会等名: The 103rd Annual Meeting of the American Urological Association
  • 発表場所: Chicago, USA
  • 年月日: 20090400
• [学会発表] Clinical implications of the MDM2 SNP309 and P53 Arg7Pro polymorphisms in transitional cell carcinoma of the bladder (2009)
  • 著者名/発表者名: Horikawa Y., et al.
  • 学会等名: The 103rd Annual Meeting of the American Urological Association
  • 発表場所: Chicago, USA
  • 年月日: 20090400
• [学会発表] Prognostic significance of HIF-1alpha polymorphisms in transitional cell carcinoma of the bladder (2008)
  • 著者名/発表者名: Nadaoka J., et al.
  • 学会等名: The 102nd Annual Meeting of the American Urological Association
  • 発表場所: Orlando, USA
  • 年月日: 20080500
• [学会発表] A mutant allele in a miR-181 binding-site of the Mel-18 gene is associated with a poor prognosis in prostate cancer (2008)
  • 著者名/発表者名: Wang W., et al.
  • 学会等名: The 102nd Annual Meeting of the American Urological Association
  • 発表場所: Orlando, USA
  • 年月日: 20080500
• [学会発表] Intravesical administration of gammadelta T cells successfully prevents the growth of bladder cancer (2008)
  • 著者名/発表者名: Yuasa T., et al.
  • 学会等名: The 102nd Annual Meeting of the American Urological Association
  • 発表場所: Orlando, USA
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• [学会発表] Natural Killer T (NKT) cell ligand alpha-galactosylceramide inhibits tumor growth of murine renal cell carcinoma (2007)
  • 著者名/発表者名: Inoue T., et al.
  • 学会等名: The 101st Annual Meeting of the American Urological Association
  • 発表場所: Anaheim, USA
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• [学会発表] Low concentration of a histone deacetylase inhibitor, depsipeptide (FK228), enhances the effect of gemcitabine and docetaxel in hormone refractory prostate cancer cells (2007)
  • 著者名/発表者名: Kanzaki M., et al.
  • 学会等名: The 101st Annual Meeting of the American Urological Association
  • 発表場所: Anaheim, USA
  • 年月日: 20070500
• [学会発表] Clinial implication of vascular endothelial growth factor (VEGF) T-460C polymorphism in the risk and progression of prostate cancer (2007)
  • 著者名/発表者名: Narita S., et al.
  • 学会等名: The 101st Annual Meeting of the American Urological Association
  • 発表場所: Anaheim, USA
  • 年月日: 20070500
• [学会発表] Identifying genetic polymorphisms which predict adverse effects of MVAC in patients with urothelial cancers (2007)
  • 著者名/発表者名: Tsuchiya, N., et al.
  • 学会等名: The 101st Annual Meeting of the American Urological Association
  • 発表場所: Anaheim, USA
  • 年月日: 20070500
• [学会発表] A novel third generation bisphosphonate, minodronic acid, augments the interferon α/β-mediated inhibition of renal cell cancer cell growth both in vitro and in vivo (2007)
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  • 学会等名: The 101st Annual Meeting of the American Urological Association
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• [図書] 泌尿器がん(西條長宏, 西尾和人(編))がん化学療法・分子標的療法 uprdate (2009)
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  • 出版者: 中外医学社
• [図書] 膀胱がん・上部尿路上皮がん. 新臨床腫瘍学(改訂第2版)、編集 : 日本臨床腫瘍学会 (2009)
  • 著者名/発表者名: 羽渕友則
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• [備考] ホームページ等
  • URL: http://www.med.akita-u.ac.jp/~hinyoki/default.html