ELUCIDATION OF MOLECULAR MECHANISMS UNDERLINING THE PROGRESSION OF PROSTATE CANCER ASSOCIATED WITH HIGH-FAT DIET

2009 Fiscal Year Final Research Report

• Project/Area Number: 19390411
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Akita University
• Principal Investigator: HABUCHI Tomonori Akita University, 大学院・医学系研究科, 教授 (00293861)
• Co-Investigator(Kenkyū-buntansha): SUZUKI Akira 九州大学, 生体防御研究所, 教授 (10311565) ; NAKAMURA Akira 秋田大学, 大学院・医学系研究科, 教授 (20155815) ; OYAMA Chikara 弘前大学, 大学院・医学系研究科, 教授 (80282135) ; TSUCHIYA Norihiko 秋田大学, 大学院・医学系研究科, 准教授 (70282176) ; YUASA Takeshi 財団法人癌研究会, 附属病院化学療法科, 医長 (00314162)
• Project Period (FY): 2007 – 2009
• Keywords: 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

Research Abstract

The purpose of this study project is to delineate the molecular mechanisms underlying the progression of prostate cancer associated with high-fat diet, and to identify molecular targets to prevent the high-fat associated progression of prostate cancer. As results, we found that the tumor growth of the LNCaP xenograft was markedly enhanced by high-fat diet. The several candidate target genes associated with the high-fat diet associated progression were identified and confirmed by using microarray mRNA expression and quantitative RTPCR. Next, we focused on the TWEAK-Fn14 signal system as a target. We found that the TWEAK-Fn14 signal promote invasion and progression of prostate cancers in vitro and in clinical settings.

Research Products

• [Journal Article] Relationship Between Bone Mineral Density and Androgen-deprivation Therapy in Japanese Prostate Cancer Patients (2010)
  • Author(s): Yuasa T, Maita S, Tsuchiya N, Ma Z, Narita S, Horikawa Y, Yamamoto S, Yonese J, Fukui I, Takahashi S, Hatake K, Habuchi T.
  • Journal Title: Urology
• [Journal Article] Cystoprostatectomy as a treatment of prostate cancer involving the bladder neck (2009)
  • Author(s): Kumazawa T, Tsuchiya N, Saito M, Inoue T, Narita S, Horikawa Y, Yuasa T, Satoh S, Kato T, Nanjyo H, Habuchi T.
  • Journal Title: Urol Int. 83(2) Pages: 141-5
• [Journal Article] Clinical significance of a single nucleotide polymorphism and allelic imbalance of matrix metalloproteinase-1 promoter region in prostate cancer (2009)
  • Author(s): Tsuchiya N, Narita S, Kumazawa T, Inoue T, Ma Z, Tsuruta H, Saito M, Horikawa Y, Yuasa T, Satoh S, Ogawa O, Habuchi T.
  • Journal Title: Oncol Rep. 22(3) Pages: 493-9
• [Journal Article] The novel tumor-suppressor Mel-18 in prostate cancer : Its functional polymorphism, expression, and clinical significance (2009)
  • Author(s): Wang W, Yuasa T, Tsuchiya N, Ma Z, Maita S, Narita S, Kumazawa T, Inoue T, Tsuruta H, Horikawa Y, Saito M, Hu W, Ogawa O, Habuchi T.
  • Journal Title: Int J Cancer 125(12) Pages: 2836-43
• [Journal Article] Prevalence of skeletal complications and their impact on survival of hormone refractory prostate cancer patients in Japan (2009)
  • Author(s): Inoue T, Segawa T, Kamba T, Yoshimura K, Nakamura E, Nishiyama H, Ito N, Kamoto T, Habuchi T, Ogawa O.
  • Journal Title: Urology 73(5) Pages: 1104-9
• [Journal Article] Intravesical administration of gammadelta T cells successfully prevents the growth of bladder cancer in the murine model (2009)
  • Author(s): Yuasa T, Sato K, Ashihara E, Takeuchi M, Maita S, Tsuchiya N, Habuchi T, Maekawa T, Kimura S.
  • Journal Title: Cancer Immunol Immunother 58(4) Pages: 493-502
• [Journal Article] Identification of mRNA splicing factors as the endothelial receptor for carbohydrate-dependent lung colonization of cancer cells (2009)
  • Author(s): Hatakeyama S, Sugihara K, Nakayama J, Akama TO, Wong SM, Kawashima H, Zhang J, Smith DF, Ohyama C, Fukuda M, Fukuda MN
  • Journal Title: Proc Natl Acad Sci USA 106(9) Pages: 3095-100
• [Journal Article] (2009)
  • Author(s): Okamoto A, Yamamoto H, Imai A, Hatakeyama S, Iwabuchi I, Yoneyama T, Hashimoto Y, Koie T, Kamimura N, Mori K, Yamaya K, Ohyama C.
  • Journal Title: Oncol Rep. 21(1) Pages: 73-9
• [Journal Article] Core3 O-glycan synthase suppresses tumor formation and metastasis of prostate carcinoma PC3 and LNCaP cells through down-regulation of alpha2beta1 integrin complex (2009)
  • Author(s): Lee SH, Hatakeyama S, Yu SY, Bao X, Ohyama C, Khoo KH, Fukuda MN, Fukuda M.
  • Journal Title: J Biol Chem. 284(25) Pages: 17157-69
• [Journal Article] Single nucleotide polymorphisms of microRNA machinery genes modify the risk of renal cell carcinoma (2008)
  • Author(s): Horikawa Y, Wood CG, Yang H, Zhao H, Ye Y, Gu J, Lin J, Habuchi T, Wu X.
  • Journal Title: Clin Cancer Res. 14(23) Pages: 7956-62
• [Journal Article] Characterization of prostate cancer detected at repeat biopsy (2008)
  • Author(s): Yuasa T, Tsuchiya N, Kumazawa T, Inoue T, Narita S, Saito M, Horikawa Y, Satoh S, Habuchi T.
  • Journal Title: BMC Urol. 8(1) Pages: 14
• [Journal Article] 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)
  • Author(s): 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.
  • Journal Title: Int J Cancer 123(11) Pages: 2574-2579
• [Journal Article] Pten deficiency in melanocytes results in resistance to hair graying and susceptibility to carcinogen-induced melanomagenesis (2008)
  • Author(s): 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.
  • Journal Title: Cancer Res. 68(14) Pages: 5760-8
• [Journal Article] Bone mineral density in Japanese prostate cancer patients under androgen-deprivation therapy (2008)
  • Author(s): Wang W, Yuasa T, Tsuchiya N, Maita S, Kumazawa T, Inoue T, Saito M, Ma Z, Obara T, Tsuruta H, Satoh S, Habuchi T.
  • Journal Title: Endocr Relat Cancer 15(4) Pages: 943-52
• [Journal Article] Association of genetic polymorphisms at 8q24 with the risk of prostate cancer in a Japanese population (2008)
  • Author(s): Terada N, Tsuchiya N, Ma Z, Shimizu Y, Kobayashi T, Nakamura E, Kamoto T, Habuchi T, Ogawa O.
  • Journal Title: Prostate 68(15) Pages: 1689-95
• [Journal Article] Normal development is an integral part of tumorigenesis in T cell-specific PTEN-deficient mice (2008)
  • Author(s): Xue L, Nolla H, Suzuki A, Mak TW, Winoto A.
  • Journal Title: Proc Natl Acad Sci USA 105(6) Pages: 2022-7
• [Journal Article] The roles of PTEN in development, physiology and tumorigenesis in mouse models : a tissue-by-tissue survey (2008)
  • Author(s): Knobbe CB, Lapin V, Suzuki A, Mak TW
  • Journal Title: Oncogene 27(41) Pages: 5398-415
• [Journal Article] Drug related genetic polymorphisms affecting adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin in patients with urothelial cancer (2008)
  • Author(s): Tsuchiya N, Inoue T, Narita S, Kumazawa T, Saito M, Obara T, Tsuruta H, Horikawa Y, Yuasa T, Satoh S, Habuchi T.
  • Journal Title: J Urol. 180(6) Pages: 2389-95
• [Journal Article] A genetic polymorphism of the osteoprotegerin gene is associated with an increased risk of advanced prostate cancer (2008)
  • Author(s): Narita N, Yuasa T, Tsuchiya N, Kumazawa T, Narita S, Inoue T, Ma Z, Saito M, Horikawa Y, Satoh S, Ogawa O, Habuchi T.
  • Journal Title: BMC Cancer 8 Pages: 224
• [Journal Article] Clinical implications of the MDM2 SNP309 and p53 Arg72Pro polymorphisms in transitional cell carcinoma of the bladder (2008)
  • Author(s): Horikawa Y, Nadaoka J, Saito M, Kumazawa T, Inoue T, Yuasa T, Tsuchiya N, Nishiyama H, Ogawa O, Habuchi T.
  • Journal Title: Oncol Rep. 20(1) Pages: 49-55
• [Journal Article] BPDE Induced Lymphocytic Chromosome 3p Deletions May Predict Renal Cell Carcinoma Risk (2008)
  • Author(s): Zhu Y, Horikawa Y, Yang H, Wood CG, Habuchi T, Wu X.
  • Journal Title: J Urol. 179(6) Pages: 2416-21
• [Journal Article] Prospective Evaluation of Selection Criteria for Active Surveillance in Japanese Patients with Stage T1cN0M0 Prostate Cancer (2008)
  • Author(s): 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.
  • Journal Title: Jpn J Clin Oncol 38(2) Pages: 122-8
• [Journal Article] Candidate genes involved in enhanced growth of human prostate cancer under high fat feeding identified by microarray analysis (2008)
  • Author(s): Narita S, Tsuchiya N, Saito M, Inoue T, Kumazawa T, Yuasa T, Nakamura A, Habuchi T.
  • Journal Title: Prostate 68(3) Pages: 321-35
• [Journal Article] Prognostic significance of HIF-1alpha polymorphisms in transitional cell carcinoma of the bladder (2008)
  • Author(s): Nadaoka J, Horikawa Y, Saito S, Kumazawa T, Inoue T, Narita S, Yuasa T, Satoh S, Nishiyama H, Ogawa O, Tsuchiya N, Habuchi T.
  • Journal Title: Int J Cancer 122(6) Pages: 1297-302
• [Journal Article] 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)
  • Author(s): Inoue T, Obara T, Saito M, Kumazawa T, Yuasa T, Matuura S, Tsuchiya N, Satoh S, Habuchi T.
  • Journal Title: Hinyokika Kiyo. 53(9) Pages: 613-8
• [Journal Article] Clinical implication of vascular endothelial growth factor T-460C polymorphism in the risk and progression of prostate cancer (2007)
  • Author(s): Fukuda H, Tsuchiya N, Narita S, Kumazawa T, Horikawa Y, Inoue T, Saito M, Yuasa T, Matsuura S, Satoh S, Ogawa O, Habuchi T.
  • Journal Title: Oncol Rep. 18(5) Pages: 1155-63
• [Journal Article] Zoledronic acid-a multiplicity of anti-cancer action (2007)
  • Author(s): Yuasa T, Kimura S, Ashihara E, Habuchi T, Maekawa T.
  • Journal Title: Curr Med Chem. 14(20) Pages: 2126-35
• [Journal Article] Lymphatic invasion is a prognostic factor for bladder cancer treated with radical cystectomy (2007)
  • Author(s): Horikawa Y, Kumazawa T, Narita S, Inoue T, Yuasa T, Matsuura S, Nanjo H, Satoh S, Tsuchiya N, Habuchi T.
  • Journal Title: Int J Clin Oncol. 12(2) Pages: 131-6
• [Journal Article] Low concentrations of the histone deacetylase inhibitor, depsipeptide, enhance the effects of gemcitabine and docetaxel in hormone refractory prostate cancer cells (2007)
  • Author(s): Kanzaki M, Kakinuma H, Kumazawa T, Inoue T, Saito M, Narita S, Yuasa T, Tsuchiya N, Habuchi T.
  • Journal Title: Oncol Rep. 17(4) Pages: 761-7
• [Presentation] 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)
  • Author(s): Narita S., et al.
  • Organizer: The 103rd Annual Meeting of the American Urological Association
  • Place of Presentation: Chicago, USA
  • Year and Date: 20090400
• [Presentation] Overexpression of BCL-2 seen in resifual prostate cancer after neoadjuvant chemohormonal therapy with docetaxel for locally advanced prostate cancer (2009)
  • Author(s): Kumazawa T., et al.
  • Organizer: The 103rd Annual Meeting of the American Urological Association
  • Place of Presentation: Chicago, USA
  • Year and Date: 20090400
• [Presentation] Clinical implications of the MDM2 SNP309 and P53 Arg7Pro polymorphisms in transitional cell carcinoma of the bladder (2009)
  • Author(s): Horikawa Y., et al.
  • Organizer: The 103rd Annual Meeting of the American Urological Association
  • Place of Presentation: Chicago, USA
  • Year and Date: 20090400
• [Presentation] Prognostic significance of HIF-1alpha polymorphisms in transitional cell carcinoma of the bladder (2008)
  • Author(s): Nadaoka J., et al.
  • Organizer: The 102nd Annual Meeting of the American Urological Association
  • Place of Presentation: Orlando, USA
  • Year and Date: 20080500
• [Presentation] A mutant allele in a miR-181 binding-site of the Mel-18 gene is associated with a poor prognosis in prostate cancer (2008)
  • Author(s): Wang W., et al.
  • Organizer: The 102nd Annual Meeting of the American Urological Association
  • Place of Presentation: Orlando, USA
  • Year and Date: 20080500
• [Presentation] Intravesical administration of gammadelta T cells successfully prevents the growth of bladder cancer (2008)
  • Author(s): Yuasa T., et al.
  • Organizer: The 102nd Annual Meeting of the American Urological Association
  • Place of Presentation: Orlando, USA
  • Year and Date: 20080500
• [Presentation] Natural Killer T (NKT) cell ligand alpha-galactosylceramide inhibits tumor growth of murine renal cell carcinoma (2007)
  • Author(s): Inoue T., et al.
  • Organizer: The 101st Annual Meeting of the American Urological Association
  • Place of Presentation: Anaheim, USA
  • Year and Date: 20070500
• [Presentation] Low concentration of a histone deacetylase inhibitor, depsipeptide (FK228), enhances the effect of gemcitabine and docetaxel in hormone refractory prostate cancer cells (2007)
  • Author(s): Kanzaki M., et al.
  • Organizer: The 101st Annual Meeting of the American Urological Association
  • Place of Presentation: Anaheim, USA
  • Year and Date: 20070500
• [Presentation] Clinial implication of vascular endothelial growth factor (VEGF) T-460C polymorphism in the risk and progression of prostate cancer (2007)
  • Author(s): Narita S., et al.
  • Organizer: The 101st Annual Meeting of the American Urological Association
  • Place of Presentation: Anaheim, USA
  • Year and Date: 20070500
• [Presentation] Identifying genetic polymorphisms which predict adverse effects of MVAC in patients with urothelial cancers (2007)
  • Author(s): Tsuchiya, N., et al.
  • Organizer: The 101st Annual Meeting of the American Urological Association
  • Place of Presentation: Anaheim, USA
  • Year and Date: 20070500
• [Presentation] 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)
  • Author(s): Yuasa, T., et al.
  • Organizer: The 101st Annual Meeting of the American Urological Association
  • Place of Presentation: Anaheim, USA
  • Year and Date: 20070500
• [Book] Prognostic Markers for bladder cancer. In : "Bladder Tumors : Molecular Aspects and Clinical Management(Edi. : Vinata B. Lokeshwar) (2010)
  • Author(s): Tomonori Habuchi
  • Publisher: Springer US(in press)
• [Book] Bladder Cancer : in Chapter 11 : Field Cancerization in Specific Cancers : IN Clinical Utility of Molecular Signatures in Cancer Fields(Edi. : Gabriel Dakubo) (2010)
  • Author(s): Tomonori Habuchi, Tadao Kakizoe
  • Publisher: Nova Science Publishing Co.(in press)
• [Book] 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)
  • Author(s): 湯浅健, 羽渕友則
  • Total Pages: 674-681
  • Publisher: 中外医学社
• [Book] 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)
  • Author(s): 羽渕友則
  • Total Pages: 552-562
  • Publisher: 南江堂
• [Remarks] ホームページ等
  • URL: http://www.med.akita-u.ac.jp/~hinyoki/default.html