Impact of the aPKC/PAR system on carcinogenesis and progression.

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590368
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Yokohama City University
• Principal Investigator: NAGASHIMA Yoji Yokohama City University, 医学研究科, 准教授 (10217995)
• Co-Investigator(Kenkyū-buntansha): AKIMOTO Kazunori 横浜市立大学, 医学部, 助教 (70285104)
• Co-Investigator(Renkei-kenkyūsha): CHISHIMA Takashi 横浜市立大学, 附属病院, 准教授 (70438141) ; ISHIKAWA Takashi 立大学, 市民総合医療ンター, 准教授 (80275049) ; UEMURA Hiroji 横浜市立大学, 附属病院, 准教授 (50244439) ; ISHIGURO Hitoshi 横浜市立大学, 医学研究科, 客員准教授 (00381666) ; KANNO Hiroshi 横浜市立大学, 医学部, 准教授 (40244496) ; AOKI Ichiro 横浜市立大学, 医学研究科, 教授 (00184028) ; INAYAMA Yoshiaki 横浜市立大学, 附属病院, 教授 (10184730) ; NOZAWA Akinori 横浜市立大学, 市民総合医療センター, 准教授 (00228321)
• Project Period (FY): 2008 – 2010
• Keywords: 細胞極性

Research Abstract

aPKCλ/ιhas a pivotal role in establishment and maintenance of cell polarity. In this study, we demonstrated that (1) aPKCλ/ιis overexpressed in various cancer cells, including breast and prostate cancers, (2) aPKCλ/ιinduces IL6 expression to obtain castration resistance in prostatic cancer (aPKC-IL6 pathway), and (3) correlation of expression of aPKCλ/ι and IL6 was demonstrated in the breast cancer as well as prostatic cancer.

Research Products

• [Journal Article] The topoisomerase II alpha gene status in primary breast cancer is a predictive marker of the response to anthracycline-based neoadjuvant chemotherapy. (2010)
  • Author(s): Kawachi K, Sasaki T, Murakami A, Ishikawa T, Kito A, Ota I, Shimizu D, Nozawa A, Nagashima Y, Machinami R, Aoki I
  • Journal Title: Pathol Res Pract 206(3) Pages: 156-162
• [Journal Article] Expression of angiotensin II type 1 receptor interacting molecule in normal human kidney and IgA nephropathy. (2010)
  • Author(s): Masuda S-I, Tamura K, Wakui H, Maeda A, Dejima T, Hirose T, Toyoda M, Azuma K, Ohsawa M, Kanaoka T, Yanagi M, Yoshida S-i, Mitsuhashi H, Matsuda M, Ishigami T, Toya Y, Suzuki D, Nagashima Y, Umemura S
  • Journal Title: Am J Physiol Renal Physiol 299(4) Pages: F720-731
• [Journal Article] Loss-of-function mutations of CHST14 in a new type of Ehlers-Danlos syndrome. (2010)
  • Author(s): Miyake N, Kosho T, Mizumoto S, Furuichi T, Hatamochi A, Nagashima Y, Arai E, Takahashi K, Kawamura R, Wakui K, Takahashi J, Kato H, Yasui H, Ishida T, Ohashi H, Nishimura G, Shiina M, Saitsu H, Tsurusaki Y, Doi H, Fukushima Y, Ikegawa S, Yamada S, Sugahara K, Matsumoto N
  • Journal Title: Hum Mutat 31(8) Pages: 966-974
• [Journal Article] A novel method for isolating podocytes using magnetic activated cell sorting. (2010)
  • Author(s): Murakami A, Oshiro H, Kanzaki S, Yamaguchi A, Yamanaka S, Furuya M, Miura S, Kanno H, Nagashima Y, Aoki I, Nagahama K
  • Journal Title: Nephrol Dial Transplant 25(12) Pages: 3884-3890
• [Journal Article] High expression of the atypical protein kinase C λ/ι in gastric cancer is promising prognostic factor for recurrence. (2010)
  • Author(s): Takagawa R, Akimoto K, Ichikawa Y, Akiyama H, Endo I, Kojima Y, Ishiguro H, Inayama Y, Aoki I, Kunisaki C, Nagashima Y, Ohno S
  • Journal Title: Ann Surg Oncol 17(1) Pages: 81-88
• [Journal Article] Expression of laminin γ2 chain monomer enhances invasive growth of human carcinoma cells in vivo. (2010)
  • Author(s): Tsubota Y, Ogawa T, Oyanagi J, Nagashima Y, Miyazaki K
  • Journal Title: Int J Cancer 127(9) Pages: 2031-2041
• [Journal Article] Expression of aquaporin 1 in primary renal tumors : A prognostic indicator for clear-cell renal cell carcinoma. (2009)
  • Author(s): Huang Y, Murakami T, Sano F, Kondo K, Nakaigawa N, Kishida T, Kubota Y, Nagashima Y, Yao M
  • Journal Title: Eur Urol 6(4) Pages: 690-698
• [Journal Article] aPKCλ/ι promotes growth of prostate cancer cells in an autocrine manner through transcriptional activation of interleukin-6. (2009)
  • Author(s): Ishiguro H, Akimoto K, Nagashima Y, Kojima Y, Sasaki T, Ishiguro-Imagawa Y, Nakaigawa N, Ohno S, Kubota Y, Uemura H
  • Journal Title: Pro Natl Acad Sci USA 106(38) Pages: 16369-16374
• [Journal Article] Enhanced effect of connexin 43 on cisplatin-induced cytotoxicity in mesothelioma cells. (2009)
  • Author(s): Sato H, Iwata H, Takano Y, Yamada R, Okuzawa H, Nagashima Y, Yamaura K, Ueno K, Yano T
  • Journal Title: J Pharmacol Sci 110(4) Pages: 466-475
• [Journal Article] Collecting duct carcinoma of the kidney : an immunohistochemical evaluation of the use of antibodies for differential diagnosis. (2008)
  • Author(s): Kojima Y, Akimoto K, Nagashima Y, Ishiguro H, Kobayashi N, Matsuzaki O, Shirai S, Aoki I, Yao M, Shima H
  • Journal Title: Hum Pathol 39(9) Pages: 1350-1359
• [Journal Article] Mutations of c-kit gene in bilateral testicular germ cell tumours in Japan. (2008)
  • Author(s): Sakuma Y, Matsukuma S, Yoshihara M, Sakurai S, Nishii M, Kishida T, Kubota Y, Nagashima Y, Inayama Y, Sasaki T, Nakamura Y, Miura T, Kameda Y, Tsuchiya E, Miyagi Y
  • Journal Title: Cancer Lett 259(2) Pages: 119-126
• [Journal Article] 5-Aza-2'-deoxycytidine suppresses human renal carcinoma cell growth in a xenograft model via up-regulation of the connexin 32 gene. (2008)
  • Author(s): Hagiwara H, Sato H, Ohde Y, Takano Y, Seki T, Ariga T, Hokaiwado N, Asamoto M, Shirai T, Nagashima Y, Yano T
  • Journal Title: Br J Pharmacol 153(7) Pages: 1373-1381
• [Journal Article] Role of nitric oxide synthesized by nitric oxide synthase 2 in liver regeneration. (2008)
  • Author(s): Kumamoto T, Togo S, Ishibe A, Morioka D, Watanabe K, Takahashi T, Shimizu T, Matsuo KI, Kubota T, Tanaka K, Nagashima Y, Kawai J, Hayashizaki Y, Shimada H
  • Journal Title: Liver Int 28(6) Pages: 865-877
• [Journal Article] Effectiveness of antiplatelet drugs against experimental non-alcoholic fatty liver disease. (2008)
  • Author(s): Fujita K, Nozaki Y, Wada K, Yoneda M, Endo H, Takahashi H, Iwasaki T, Inamori M, Abe Y, Kobayashi N, Kirikoshi H, Kubota K, Saito S, Nagashima Y, Nakajima A
  • Journal Title: Gut 57(11) Pages: 1583-1591
• [Journal Article] Antitumour effect of electrochemotherapy with bleomycin on human prostatic cancer xenograft. (2008)
  • Author(s): Ueki T, Uemura H, Nagashima Y, Ohta S, Ishiguro H, Kubota Y
  • Journal Title: Brit J Urol BJU Int 102(10) Pages: 1467-1471
• [Journal Article] Heme oxygenase 1 attenuates the development of atopic dermatitis-like lesions in mice : implications for human disease. (2008)
  • Author(s): Kirino M, Kirino Y, Takeno M, Nagashima Y, Takahashi K, Kobayashi M, Murakami S, Hirasawa T, Ueda A, Aihara M, Ikezawa Z, Ishigatsubo Y
  • Journal Title: J Allergy Clin Immunol 122(2) Pages: 290-297
• [Journal Article] Semaphorin3A alleviates skin lesions and scratching behavior in NC/Nga mice, an atopic dermatitis model.(大学院優秀論文) (2008)
  • Author(s): Yamaguchi J, Nakamura F, Aihara M, Yamashita N, Usui H, Hida T, Takei K, Nagashima Y, Ikezawa Z, Goshima Y
  • Journal Title: J Invest Dermatol 128(12) Pages: 2842-2849
• [Journal Article] Expression of adiponectin receptors, AdipoR1 and AdipoR2, in normal colon epithelium and colon cancer tissue. (2008)
  • Author(s): Yoneda K, Tomimoto A, Endo H, Iida H, Sugiyama M, Takahashi H, Mawatari H, Nozaki Y, Fujita K, Yoneda M, Inamori M, Nakajima N, Wada K, Nagashima Y, Nakagama H, Uozaki H, Fukayama M, Nakajima A
  • Journal Title: Oncol Rep 20(3) Pages: 479-488
• [Journal Article] Inhibition of peroxisome proliferator-activated receptor gamma activity suppresses pancreatic cancer cell motility. (2008)
  • Author(s): Nakajima A, Tomimoto A, Fujita K, Sugiyama M, Takahashi H, Ikeda I, Hosono K, Endo H, Yoneda K, Iida H, Inamori M, Kubota K, Saito S, Nakajima N, Wada K, Nagashima Y, Nakagama H
  • Journal Title: Cancer Sci 99(10) Pages: 1892-1900
• [Journal Article] Metformin suppresses intestinal polyp growth in Apc Min/+ mice. (2008)
  • Author(s): Tomimoto A, Endo H, Sugiyama M, Fujisawa T, Hosono K, Takahashi H, Nakajima N, Nagashima Y, Wada K, Nakagama H, Nakajima A
  • Journal Title: Cancer Sci 99(11) Pages: 2136-2141
• [Journal Article] The co-expression of aPKCλ/ι and IL-6 in prostate cancer tissue correlates with biochemical recurrence.
  • Author(s): Ishiguro H, Akimoto K, Nagashima Y, Kagawa E, Sasaki T, Sano J-y, Takagawa R, Fujinami K, Sasaki K, Aoki I, Ohno S, Kubota Y, Uemura H
  • Journal Title: Cancer Sci in press
• [Presentation] 細胞極性因子aPKCλによる上皮前駆細胞の増殖制御とその破綻 (2010)
  • Author(s): 秋本和憲, 鄭允文, 長嶋洋治, 石黒斉, 佐々木和教, 金民大, 李文武, 角和卓, 谷口英樹, 野田哲生, 大野茂男
  • Organizer: 第33回日本分子生物学会・第83回日本生化学会合同大会 ワークショップ「上皮細胞の機能とその破綻がもたらす病態のメカニズム」
  • Place of Presentation: 神戸
  • Year and Date: 20101200
• [Presentation] Atypical protein kinase Cλ/ι regulates mouse mammary progenitor cell propagation. (2010)
  • Author(s): Akimoto K, Zheng Y-W, Nagashima Y, Ishiguro H, Asai-Sato M, Kojima Y, Li B, Sasaki K, Kagawa E, Kim M, Taniguchi H, Noda T, Ohno S
  • Organizer: 6th International Symposium on Hormonal Oncogenesis
  • Place of Presentation: Tokyo
  • Year and Date: 20100900
• [Presentation] aPKC and IL-6 expression in prostate cancer tissues. (2010)
  • Author(s): 石黒斉, 秋本和憲, 長嶋洋治, 加川絵理子, 佐々木毅, 佐野仁勇, 高川亮, 佐々木和教, 藤浪潔, 青木一郎, 大野茂男, 窪田吉信, 上村博司
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 20100900
• [Presentation] 胃癌におけるaPKCλ/ιの高発現は再発の危険因子である (2010)
  • Author(s): 長嶋洋治, 山中正二, 村上あゆみ, 稲山嘉明, 青木一郎
  • Organizer: 第99回日本病理学会春季総会
  • Place of Presentation: 東京
  • Year and Date: 20100400
• [Presentation] ベリニ管癌の網羅的ゲノム解析 (2010)
  • Author(s): 井上享, 成松隆弘, 中田知里, 松浦恵子, 佐藤文憲, 長嶋洋治, 矢尾正祐, 窪田吉信, 羽渕友則、大山力, 西山博之、小川修, 中川正之, 守山正胤, 三股浩光
  • Organizer: 第19回泌尿器科分子・細胞研究会
  • Place of Presentation: 神戸
  • Year and Date: 20100200
• [Presentation] The overexpression of the atypical protein kinase C λ/ι in malignant melanoma correlates with its undifferentiation state and metastatic ability. (2009)
  • Author(s): Miwa H, Akimoto K, Inoue Y, Wada H, Ishiguro H, Ohno S, Nagashima Y, Ikezawa Z
  • Organizer: 34th Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: 福岡
  • Year and Date: 20091200
• [Presentation] Endothelial nitric oxide synthase changes the fat distribution in high-fat diet-induced NAFLD mice. (2009)
  • Author(s): Nozaki Y, Fujita K, Yoneda M, Mawatari H, Shinohara Y, Imajo K, Endo H, Hosono K, Yakahashi H, Kirikoshi H, Abe Y, Kobayashi N, Inamori M, Kubota K, Nagashima Y, Saito S, Nakajima A
  • Organizer: GASTRO2009 UEGW/WCOG
  • Place of Presentation: London
  • Year and Date: 20091100
• [Presentation] Expression of the atypical protein kinase C in lateral spreading type tumors of the colon or the rectum. (2009)
  • Author(s): Ichikawa Y, Kojima Y, Nagashima Y, Akimoto K, Ishikawa T, Goto A, Hirokawa S, Yamagishi S, Ota M, Fujii S, Nakajima A, Endo I, Ohno S
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 20091000
• [Presentation] Clinical significance of typical protein kinase iota expression in gastric cancer. (2009)
  • Author(s): Takagawa R, Nagashima Y, Akimoto K, Akiyama H, Ono H, Kimura J, Ichikawa Y, Endo I
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 20091000
• [Presentation] Construction of the gene expression signature model for predict of patient outcome with clear cell renal carcinoma. (2009)
  • Author(s): Huang Y, Murakami T, Sano F, Kondo K, Nakaigawa N, Kishida T, Kuboya Y, Nagashima Y, Yao M
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 20091000
• [Presentation] The overexpression and altered localization of the atypical protein kinase C λ/ι in breast cancers. (2009)
  • Author(s): 長嶋洋治, 稲山嘉明, 山中正二, 佐々木毅, 青木一郎
  • Organizer: 第56回日本臨床検査医学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 20090800
• [Presentation] Expression of the atypical protein kinase C in lateral spreading type tumors of the colon or the rectum. (2009)
  • Author(s): Ichikawa Y, Kojima Y, Ishikawa T, Shimizu D, Goto A, Hirokawa S, Kijima M, Yamamoto H, Suwa H, Yamagishi S, Osada S, Ota M, Fujii S, Endo I, Shimada H, Akimoto K, Nagashima Y, Ohno S
  • Organizer: 100th Annual Meeting of American Association for Cancer Research
  • Place of Presentation: Denver
  • Year and Date: 20090400
• [Presentation] Improvement of sensitivity to vinblastine by restoration of connexin 32 gene in renal cell carcinoma cells. (2009)
  • Author(s): Takano Y, Iwata H, Sato H, Okuzawa H, Yamada R, Nagashima Y, Yamaura K, Ueno K, Yano T
  • Organizer: 100th Annual Meeting of American Association for Cancer Research
  • Place of Presentation: Denver
  • Year and Date: 20090400
• [Presentation] 腎癌におけるaquapolin 1遺伝子発現とその診断的有用性,臨床応用についての検討 (2009)
  • Author(s): 矢尾正祐, 黄榮, 村上貴之, 佐野太, 近藤慶一, 中井川昇, 岸田健, 長嶋洋治, 窪田吉信
  • Organizer: 第97回日本泌尿器科学会総会
  • Place of Presentation: 岡山
  • Year and Date: 20090400
• [Presentation] 淡明細胞型腎癌におけるMET蛋白の機能の多様性 (2009)
  • Author(s): 中井川昇, 矢尾正祐, 和田朋子, 長嶋洋治, 窪田吉信
  • Organizer: 第97回日本泌尿器科学会総会
  • Place of Presentation: 岡山
  • Year and Date: 20090400
• [Presentation] 透析腎癌の網羅的ゲノム解析 (2009)
  • Author(s): 吉本多一郎, 松浦恵子, 中田知里, 成松隆弘, 井上享, 瀬戸加大, 長嶋洋治, 佐藤文憲, 守山正胤, 三股浩光
  • Organizer: 第97回日本泌尿器科学会総会
  • Place of Presentation: 岡山
  • Year and Date: 20090400
• [Presentation] 前立腺癌におけるaPKCの発現と前立腺癌進展機構 (2009)
  • Author(s): 石黒斉, 秋本和憲, 長嶋洋治, 小島康幸, 佐々木毅, 上村博司, 大野茂男, 窪田吉信
  • Organizer: 第97回日本泌尿器科学会総会
  • Place of Presentation: 岡山
  • Year and Date: 20090400
• [Presentation] A three gene expression signature model to predict clinical outcome of clear cell renal carcinoma. (2009)
  • Author(s): Huang Y, Shioi K, Hattori K, Murakami T, Sano, Baba M, Kondo K, Nakaigawa N, Kishida T, Nagashima Y, Kubota Y, Yao M
  • Organizer: The 2nd International Workshop co-sponsored by Yokohama City University and FDA (United States Food and Drug Administration). Biomarkers for development of biological products and new therapy.
  • Place of Presentation: Yokohama
  • Year and Date: 20090300
• [Presentation] The role of aPKC lambda in prostate cancer progression. (2008)
  • Author(s): Ishiguro H, Akimoto K, Nagashima Y, Kojima Y, Ishiguro Y, Sasaki T, Uenura H, Ohno S, Kubota Y
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 20081000
• [Presentation] The status of aPKCλ/ι in breast cancer correlates with the pathologic types. (2008)
  • Author(s): 長嶋洋治, 稲山嘉明, 佐々木毅, 大城久, 村上あゆみ, 山中正二, 河内香江, 野澤昭典, 青木一郎
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢
  • Year and Date: 20080500
• [Book] Molecular mechanism and Morphology in Cancer(Pathology and molecular biology of renal neoplasms. Recent advances and impacts on pathological classification.)(Nakamura M, Kakudo K (eds.)) (2009)
  • Author(s): Nagashima Y, Kobayashi N, Kagawa E, Aoki I, Inayama Y, Yao M
  • Total Pages: 12-41
  • Publisher: Bentham Science Publishers E-Book
• [Remarks] ホームページ等
  • URL: http://www-user.yokohama-cu.ac.jp/~byori2/index.html