Study on molecular carcinogenesis in transient amplifying cell of human prostate

2009 Fiscal Year Final Research Report

• Project/Area Number: 19390104
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Nara Medical University
• Principal Investigator: KONISHI Noboru Nara Medical University, 医学部, 教授 (20145832)
• Co-Investigator(Kenkyū-buntansha): SHIMADA Keiji 奈良県立医科大学, 医学部, 講師 (90336850)
• Project Period (FY): 2007 – 2009
• Keywords: 前立腺 / 癌化 / 組織幹細胞 / senescence / transient amplifying cell / junB

Research Abstract

Transient amplifying (TA) cells are a subset of basal cell populations within the prostate from which cancers are thought to originate. Most TA cell populations showed increased expression of p53, p21, p16, and pRb, resulting in senescence. However, TA cell clones with reduced p16 expression successfully bypassed this phase. The close correlation was found between the levels of junB and p16 expression. Transfection of junB siRNA in prostatic TA cells allowed the cells to escape senescence, presumably through inactivation of p16/pRb ; this suggests that activation of junB/p16/pRb is required to block clonal expansion. Interestingly, the percentage of peripheral zone TA cells evading senescence was significantly higher than those from central and transition zones. Metastatic prostate tumors, as well as prostate cancers with high Gleason scores, demonstrated significantly low junB immunopositivity. junB thus apparently plays an important role in controlling prostate carcinogenesis and may be a new target for cancer prevention and therapy.

Research Products

• [Journal Article] Technical acquisition and dosimetric assessment of iodine-125 permanent brachytherapy in a series of 100 patients with localized prostate cancer: our first series of 100 patients (2009)
  • Author(s): Tanaka, N., Asakawa, I., Kondo, H. Tanaka, M., Fujimoto, K., Hasegawa, M., Konishi, N., Hirao, Y
  • Journal Title: Int. J. Urology Vol.16(1) Pages: 70-74
  • Peer Reviewed
• [Journal Article] Isoflurane exerts a short-term but not a long-term preconditioning effect in neonatal rats exposed to a hypoxic-ischaemic neuronal injury (2009)
  • Author(s): Sasaoka, N., Kawaguchi, M., Kawaraguchi, Y., Nakamura, M., Konishi, N., Patel, H., Patel, P.M., Furuya, H.
  • Journal Title: Acta Anaesthesiol Scand Vol.53(1) Pages: 46-54
  • Peer Reviewed
• [Journal Article] Immunohistochemical analysis of neuroendocrine differentiation in prostate cancer (2009)
  • Author(s): Ishida, E., Nakamura, M., Shimada, K., Tasaki, M., Konishi, N.
  • Journal Title: Pathobiology Vol.76(1) Pages: 30-38
  • Peer Reviewed
• [Journal Article] A novel human AlkB homologue, ALKBH8, contributes to human bladder cancer progression (2009)
  • Author(s): Shimada, K., Nakamura, M., Anai, S., De Velasco, M., Tanaka, M., Tsujikawa, K., Ouji, Y., Konishi, N.
  • Journal Title: Cancer Res Vol.69(7) Pages: 3157-3164
  • Peer Reviewed
• [Journal Article] A case of urothelial carcinoma with triple variants featuring nested, plasmacytoid, and lipoid cell morphology (2009)
  • Author(s): Shimada, K., Nakamura, M., Konishi, N.
  • Journal Title: Diagn Cytopathol Vol.37(4) Pages: 272-276
  • Peer Reviewed
• [Journal Article] Syndecan-1, a new target molecule involved in progression of androgen-independent prostate cancer (2009)
  • Author(s): Shimada, K., Nakamura, M., De Velasco, M.A., Tanaka, M., Ouji, Y., Konishi, N.
  • Journal Title: Cancer Sci Vol.100(7) Pages: 1248-1254
  • Peer Reviewed
• [Journal Article] Variations in international prostate symptom scores, uroflowmetric parameters, and prostate volume after 1251 permanent brachytherapy for localized prostate cancer (2009)
  • Author(s): Tanaka, N., Fujimoto, K., Hirao, Y., Asakawa, I., Hasegawa, M., Konishi, N.
  • Journal Title: Urology Vol.74(2) Pages: 407-411
  • Peer Reviewed
• [Journal Article] Protein kinase Cγ, a protein causative for dominant ataxia, negatively regulates nuclear import of recessive-ataxia-related aprataxin (2009)
  • Author(s): Asai, H., Hirano, M., Shimada, K., Kiriyama, T., Furiya, Y., Ikeda, M., Iwamoto, T., Mori, T., Nishinaka, K., Konishi, N., Udaka, F., Ueno, S.
  • Journal Title: Hum Mol Genet Vol.18(19) Pages: 3533-3543
  • Peer Reviewed
• [Journal Article] Phosphorylation status of fas-associated, death domain-containing protein regulates telomerase activity and strongly correlates with prostate cancer outcomes (2009)
  • Author(s): Matsumura, Y., Shimada, K., Tanaka, N., Fujimoto, K., Hirao, Y., Konishi, N.
  • Journal Title: Pathobiology Vol.76(6) Pages: 293-302
  • Peer Reviewed
• [Journal Article] Clinical importance of B7-H3 expression in human pancreatic cancer (2009)
  • Author(s): Yamato, I., Sho, M., Nomi, T., Akahori, T., Shimada, K., Hotta, K., Kanehiro, H., Konishi, N., Yagita, H., Nakajima, V.
  • Journal Title: Br J Cancer Vol.101(10) Pages: 1709-1716
  • Peer Reviewed
• [Journal Article] The long-term effects of mild to moderate hypothermia on gray and white matter injury after spinal cord ischemia in rats (2009)
  • Author(s): Horiuchi, T., Kawaguchi, M., Kurita, N., Inoue, S., Nakamura, M., Konishi, N., Furuya, H.
  • Journal Title: Anesth Analg Vol.109(2) Pages: 559-566
  • Peer Reviewed
• [Journal Article] HRK inactivation associated with promoter methylation and LOH in prostate cancer (2008)
  • Author(s): Higuchi, T., Nakamura, M., Shimada, K., Ishida, E., Hirao, K., Konishi, N.
  • Journal Title: Prostate Vol.68(1) Pages: 105-113
  • Peer Reviewed
• [Journal Article] Prostate cancer antigen-1 contributes to cell survival and invasion though discoidin receptor 1 in human prostate cancer (2008)
  • Author(s): Shimada, K., Nakamura, M., Ishida, E., Higuchi, T., Yamamoto, H., Tsujikawa, K., Konishi, N.
  • Journal Title: Cancer Sci Vol.99 Pages: 39-45
  • Peer Reviewed
• [Journal Article] 尿路系腫瘍をめぐる諸問題尿路上皮癌の分子病理をめぐって, 病理と臨床 (2008)
  • Author(s): 島田啓司, 小西登
  • Journal Title: 文光堂 第26巻第2号 Pages: 133-139
  • Peer Reviewed
• [Journal Article] Cancer stem cell theroyと前立腺癌, 病理と臨床 (2008)
  • Author(s): 小西登
  • Journal Title: 文光堂 第26巻第6号 Pages: 626-627
• [Journal Article] Function of JunB in transient amplifying cell senescence and progression of human prostate cancer (2008)
  • Author(s): Konishi, N., Shimada, K., Nakamura, M., Ishida, E., Ota, I., Tanaka, N., Fujimoto, K.
  • Journal Title: Clin Cancer Res Vol.14(14) Pages: 4408-4416
  • Peer Reviewed
• [Journal Article] 特集前立腺がんの診療(精巣腫瘍を含む)1, 前立腺がんを疑うとき上検査の進め方3)Gleason score (2007)
  • Author(s): 島田啓司, 小西登
  • Journal Title: 臨床腫瘍プラクティス Vol.3(3) Pages: 253-257
• [Journal Article] c-Jun NH2 terminal kinase activation and decreased expression of mitogen-activated protein kinase phosphatase-1 play important roles in invasion and angiogenesis of urothelial carcinomas (2007)
  • Author(s): Shimada, K., Nakamura, M., Ishida, E., Higuchi, T., Tanaka, M., Ota, I., Konishi, N.
  • Journal Title: Am J Pathol Vol.171(3) Pages: 1003-1012
  • Peer Reviewed
• [Journal Article] Expression and sub-cellular localization of human ABH family molecules (2007)
  • Author(s): Tsujikawa, K., Koike, K., Kitae, K., Shinkawa, A., Arima, H., Suzuki, T., Tsuchiya, M., Makino, Y., Furukawa, T., Konishi, N., Yamamoto, H.
  • Journal Title: J Cell Mol Med Vol.11(5) Pages: 1105-1116
  • Peer Reviewed
• [Presentation] 前立腺全摘標本における分子生物学的生化学的再発予測因子の検討 (2009)
  • Author(s): 穴井智, 池田朋博, 松村善昭, 三宅牧人, 冨岡厚志, 田中宣道, 藤本清秀, 平尾佳彦, 島田啓司, 小西登
  • Organizer: 第97回日本泌尿器科学会総会
  • Place of Presentation: 岡山
  • Year and Date: 20090416-20090419
• [Presentation] 年齢別PSAカットオフ値および体積・年齢別生検本数ノモグラムを用いた前立腺生検の試み (2009)
  • Author(s): 田中宣道, 壬生寿一, 冨岡厚志, 平尾周也, 田中雅博, 永吉純一, 吉井将人, 仲川嘉紀, 渡辺秀次, 藤本清秀, 平尾佳彦, 島田啓司, 小西登
  • Organizer: 第97回日本泌尿器科学会総会
  • Place of Presentation: 岡山
  • Year and Date: 20090416-20090419
• [Presentation] Syndecan-1(CD138)を介した前立腺癌進展メカニズムの検討 (2009)
  • Author(s): 島田啓司, 中村光利, Marco A. De Velasco, 田中基幹, 小西登
  • Organizer: 第25回前立腺シンポジウム
  • Place of Presentation: 東京(他2演題)
  • Year and Date: 2009-12-12
• [Presentation] Analysis of the genes associated with premature senescence in prostate cancer and stromal cells of treated cases (2009)
  • Author(s): Ishida, E., Nakamura, M., Shimada, K., Tasaki, M., Ohshima, M., Konishi, N.
  • Organizer: 第68回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-02
• [Presentation] The phosphorylation status of FADD in biopsy specimens is associated with biochemical recurrence after prostatectomy (2009)
  • Author(s): Ikeda, T., Shimada, K., Tanaka, N., Matsumura, Y., Miyake, M., Anai, S., Tomioka, A., Okajima, E., Fujimoto, K., Hirao, Y., Konishi, N.
  • Organizer: 第68回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-02
• [Presentation] The role of syndecan-1 (CD138) in progression of human urinary bladder cancer (2009)
  • Author(s): Shimada, K., Nakamura, M., Marco A. De Velasco, Tanaka, M., Konishi, N.
  • Organizer: 第68回日本癌学会総会
  • Place of Presentation: 横浜(他3演題)
  • Year and Date: 2009-10-02
• [Presentation] 膀胱癌におけるCD138(Syndecan-1)発現の分子病理学的意義について (2009)
  • Author(s): 島田啓司, 中村光利, 田崎正人, 小西登
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 京都(他5演題)
  • Year and Date: 2009-05-02
• [Presentation] Human ABH-8 is a new molecule for the development of bladder cancer (2008)
  • Author(s): Shimada, K., Nakamura, M., Tasaki, M., Anal, S., Tanaka, M., Tsujikawa, K., Konishi, N.
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋(他2演題)
  • Year and Date: 2008-10-28
• [Presentation] 前立腺癌新規遺伝子PCA-1の機能解析 (2008)
  • Author(s): 樋日智紀, 島田啓司, 石田英和, 中村光利, 小西登
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢
  • Year and Date: 2008-05-16
• [Presentation] 前立腺progenitor cellの生物学的特性と病理組織学的意義について (2008)
  • Author(s): 島田啓司, 中村光利, 石田英和, 樋日智紀, 小西登
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢(他1演題)
  • Year and Date: 2008-05-15
• [Presentation] 膀胱尿路上皮癌における新規浸潤メカニズムの解析 (2007)
  • Author(s): 島田啓司, 中村光利, 石田英和, 樋日智紀, 田中基幹, 小西登
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜(他6演題)
  • Year and Date: 2007-10-03
• [Presentation] 前立腺癌における神経内分泌化の検討 (2007)
  • Author(s): 石田英和, 中村光利, 島田啓司, 松吉修一, 樋日智紀, 小西登
  • Organizer: 第96回日本病理学会総会
  • Place of Presentation: 大阪(他2演題)
  • Year and Date: 2007-03-14
• [Book] 腫瘍病理鑑別診断アトラス前立腺癌 (2009)
  • Author(s): 白石泰三, 他編、小西登
  • Total Pages: 9-14
  • Publisher: 文光堂
• [Book] 解明病理学病気のメカニズムを解く (2009)
  • Author(s): 青笹克之編、小西登
  • Total Pages: 451-468
  • Publisher: 医歯薬出版
• [Book] インフォームドコンセントのための図説シリーズ前立腺がん (2008)
  • Author(s): 吉田修(監修)、大薗誠一郎、荒井陽一(編)、小西登
  • Total Pages: 40-45
  • Publisher: 医薬ジャーナル
• [Remarks]
  • URL: http://www.naramed-u.ac.jp/~2path/gyouseki.html
• [Patent(Industrial Property Rights)] 膵臓癌の予防・治療剤及びそのスクリーニング方法並びに診断剤 (2009)
  • Inventor(s): 小西登
  • Industrial Property Rights Holder: リンク・ジェノミクス
  • Industrial Property Number: 特願・2009-144760
  • Filing Date: 2009-06-17
  • Acquisition Date: 2009-06-17