Identification of molecular targets for cancer therapeutics through the analysis of tumor formation in mouse models for human carcinogenesis

2009 Fiscal Year Final Research Report

• Project/Area Number: 17013006
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Japanese Foundation For Cancer Research
• Principal Investigator: NODA Tetsuo Japanese Foundation For Cancer Research, 癌研究所, 所長 (10183550)
• Co-Investigator(Kenkyū-buntansha): YAO Ryoji 財団法人癌研究会, 癌研究所細胞生物部, 主任研究員 (80291095) ; YAGINUMA Katsuyuki 財団法人癌研究会, 癌研究所細胞生物部, 研究員 (40182307) ; TAKANO Hiroshi 財団法人癌研究会, 細胞生物部, 研究員 (00241555) ; SUGAWARA Minoru 東北大学, 大学院・医学系研究科, 准教授 (20311558)
• Project Period (FY): 2005 – 2009
• Keywords: 遺伝学 / 遺伝子 / 癌 / ゲノム / シグナル / モデル動物

Research Abstract

In this study, we have developed several mouse models simulating the process of human carcinogenesis induced by the activation of oncogenic signaling such as Wnt and Sonic hedgehog signaling. Through the analysis of tumor formation in these mouse models, we could have successfully elucidated the molecular mechanisms of carcinogenesis. Functional roles of cancer related genes elucidated through this analysis could suggest strong candidates for novel molecular targets of human cancer therapy.

Research Products

• [Journal Article] Deficiency of the Erc/mesothelin gene ameliorates renal carcinogenesis in Tsc2 knockout mice. (2011)
  • Author(s): D.Zhang, T.Kobayashi, T.Kojima, K.Kanenishi, Y.Hagiwara, M.Abe, H.Okura, Y.Hamano, G.Sun, M.Maeda, K.I.Jishage, T.Noda, O.Hino.
  • Journal Title: Cancer Sci. in press.
  • Peer Reviewed
• [Journal Article] Appearance of an oocyte activation-related substance during spermatogenesis in mice and humans. (2010)
  • Author(s): C.Ito, K.Yamatoya, K.Yoshida, K.Kyono, R.Yao, T.Noda, K.Toshimori.
  • Journal Title: Hum.Reprod. 25(11) Pages: 2734-2744
  • Peer Reviewed
• [Journal Article] Prospective randomized phase II study determines the clinical usefulness of genetic biomarkers for sensitivity to primary chemotherapy with paclitaxel in breast cancer. (2010)
  • Author(s): Y.Ito, K.Nagasaki, Y.Miki, T.Iwase, F.Akiyama, M.Matsuura, R.Horii, M.Makita, N.Tokudome, M.Ushijima, M.Yoshimoto, S.Takahashi, T.Noda, K.Hatake.
  • Journal Title: Cancer Sci. 102(1) Pages: 130-136
  • Peer Reviewed
• [Journal Article] Identifying molecular markers for chemosensitivity to gemcitabine in pancreatic cancer : Increased expression of interferon-stimulated gene 15 kd is associated with intrinsic chemoresistance. (2010)
  • Author(s): S.Ina, S.Hirono, T.Noda, H.Yamaue.
  • Journal Title: Pancreas 39(4) Pages: 473-485
  • Peer Reviewed
• [Journal Article] Molecular markers associated with lymph node metastasis in pancreatic ductal adenocarcinoma by genome-wide expression profiling. (2010)
  • Author(s): S.Hirono, H.Yamaue, Y.Hoshikawa, S.Ina, M.Tani, M.Kawai, M.Ushijima, M.Matsuura, Y.Saiki, A.Saiura, J.Yamamoto, Y.Miki, T.Noda.
  • Journal Title: Cancer Sci. 101(1) Pages: 259-266
  • Peer Reviewed
• [Journal Article] Newly synthesized curcumin analog has improved potential to prevent colorectal carcinogenesis in vivo. (2009)
  • Author(s): H.Shibata, H.Yamakoshi, A.Sato, H.Ohori, Y.Kakudo, C.Kudo, Y.Takahashi, M.Watanabe, H.Takano, C.Ishioka, T.Noda, Y.Iwabuchi.
  • Journal Title: Cancer Sci. 100(5) Pages: 956-960
  • Peer Reviewed
• [Journal Article] An essential role of the universal polarity protein, aPKClambda, on the maintenance of podocyte slit diaphragms. (2009)
  • Author(s): T.Hirose, D.Satoh, H.Kurihara, C.Kusaka, H.Hirose, K.Akimoto, T.Matsusaka, I.Ichikawa, T.Noda, S.Ohno.
  • Journal Title: PLoS ONE 4(1) Pages: e4194
  • Peer Reviewed
• [Journal Article] Kinetochore stretching inactivates the spindle assembly checkpoint. (2009)
  • Author(s): K.S.Uchida, K.Takagaki, K.Kumada, Y.Hirayama, T.Noda, T.Hirota.
  • Journal Title: J.Cell Biol. 184(3) Pages: 383-390
  • Peer Reviewed
• [Journal Article] Bach1 inhibits oxidative stress-induced cellular senescence by impeding p53 function on chromatin.Nat. (2008)
  • Author(s): Y.Dohi, T.Ikura, Y.Hoshikawa, Y.Katoh, K.Ota, A.Nakanome, A.Muto, S.Omura, T.Ohta, A.Ito, M.Yoshida, T.Noda, K.Igarashi.
  • Journal Title: Struct.Mol.Biol. 15(12) Pages: 1246-1254
  • Peer Reviewed
• [Journal Article] IL12RB2 and ABCA1 genes are associated with susceptibility to radiation dermatitis. (2008)
  • Author(s): M.Isomura, N.Oya, S.Tachiiri, Y.Kaneyasu, Y.Nishimura, T.Akimoto, M.Hareyama, T.Sugita, N.Mitsuhashi, T.Yamashita, M.Aoki, H.Sai, Y.Hirokawa, K.Sakata, K.Karasawa, A.Tomida, T.Tsuruo, Y.Miki, T.Noda, M.Hiraoka.
  • Journal Title: Clin.Cancer Res. 14(20) Pages: 6683-6689
  • Peer Reviewed
• [Journal Article] HOXB2, an adverse prognostic indicator for stage I lung adenocarcinomas, promotes invasion by transcriptional regulation of metastasis-related genes in HOP-62 non-small cell lung cancer cells. (2008)
  • Author(s): K.Inamura, Y.Togashi, H.Nionomiya, T.Shimoji, T.Noda, Y.Ishikawa.
  • Journal Title: Anticancer Res. 28(4B) Pages: 2121-2128
  • Peer Reviewed
• [Journal Article] Osteoporotic bone formation in mice lacking tob2 ; involvement of Tob2 in RANK ligand expression and osteoclasts differentiation. (2008)
  • Author(s): R.Ajima, T.Akiyama, M.Usui, M.Yoneda, Y.Yoshida, T.Nakamura, O.Minowa, M.Noda, S.Tanaka, T.Noda, T.Yamamoto.
  • Journal Title: FEBS Lett. 582(9) Pages: 1313-1318
  • Peer Reviewed
• [Journal Article] Biphasic response of pancreatic beta-cell mass to ablation of TSC2 in mice. (2008)
  • Author(s): Y.Shigeyama, T.Kobayashi, Y.Kido, N.Hashimoto, S.I.Asahara, T.Matsuda, A.Takeda, T.Inoue, Y.Shibutani, M.Koyanagi, T.Uchida, M.Inoue, O.Hino, M.Kasuga, T.Noda.
  • Journal Title: Mol.Cell.Biol. 28(9) Pages: 2971-2979
  • Peer Reviewed
• [Journal Article] HOXB2 as a novel prognostic indicator for stage I lung adenocarcinomas. (2007)
  • Author(s): K.Inamura, Y.Togashi, M.Okui, H.Ninomiya, M.Hiramatsu, Y.Satoh, S.Okumura, K.Nakagawa, T.Shimoji, T.Noda, Y.Ishikawa.
  • Journal Title: J.Thorac.Oncol. 2(9) Pages: 802-807
  • Peer Reviewed
• [Journal Article] α-Catenin is essential in intestinal adenoma formation. (2007)
  • Author(s): H.Shibata, H.Takano, M.Ito, H.Shioya, M.Hirota, H.Matsumoto, Y.Kakudo, C.Ishioka, T.Akiyama, Y.Kanegae, I.Saito, T.Noda.
  • Journal Title: Proc.Natl.Acad.Sci.USA 104(46) Pages: 18199-18204
  • Peer Reviewed
• [Journal Article] A metastatic signature in entire lung adenocarcinomas irrespective of morphological heterogeneity. (2007)
  • Author(s): K.Inamura, T.Shimoji, H.Ninomiya, M.Hiramatsu, M.Okui, Y.Satoh, S.Okumura, K.Nakagawa, T.Noda, M.Fukayama, Y.Ishikawa.
  • Journal Title: Hum.Pathol. 38(5) Pages: 702-709
  • Peer Reviewed
• [Journal Article] TACC3 is required for the proper mitosis of sclerotome mesenchymal cells during formation of the axial skeleton. (2007)
  • Author(s): R.Yao, Y.Natsume, T.Noda.
  • Journal Title: Cancer Sci. 98(4) Pages: 555-562
  • Peer Reviewed
• [Journal Article] Inactivation of aPKC λ results in the loss of adherens junctions in neuroepithelial cells without affecting neurogenesis in mouse neocortex. (2006)
  • Author(s): F.Imai, S.Hirai, K.Akimoto, H.Koyama, T.Miyata, M.Ogawa, S.Noguchi, T.Sasaoka, T.Noda, S.Ohno.
  • Journal Title: Development 133(9) Pages: 1735-1744
  • Peer Reviewed
• [Journal Article] Ablation of PDK1 in pancreatic beta cells induces diabetes as a result of loss of beta cell mass. (2006)
  • Author(s): N.Hashimoto, Y.Kido, T.Uchida, S.Asahara, Y.Shigeyama, T.Matsuda, A.Takeda, D.Tsuchihashi, A.Nishizawa, W.Ogawa, Y.Fujimoto, H.Okamura, K.C.Arden, P.L.Herrera, T.Noda, M.Kasuga.
  • Journal Title: Nat.Genet. 38(5) Pages: 589-593
  • Peer Reviewed
• [Journal Article] The selective continued linkage of centromeres through mitosis to interphase in the absence of mammalian separase. (2006)
  • Author(s): K.Kumada, R.Yao, T.Kawaguchi, M.Karasawa, Y.Hoshikawa, K.Ichikawa, Y.Sugitani, I.Imoto, J.Inazawa, M.Sugawara, M.Yanagida, T.Noda.
  • Journal Title: J.Cell Biol. 172(6) Pages: 835-846
  • Peer Reviewed
• [Journal Article] PAR3 is essential for cyst-mediated epicardial development by establishing apical cortical domains. (2006)
  • Author(s): T.Hirose, M.Karasawa, Y.Sugitani, M.Fujisawa, K.Akimoto, S.Ohno, T.Noda.
  • Journal Title: Development 133(7) Pages: 1389-1398
  • Peer Reviewed
• [Journal Article] VEGF receptor 1 signaling is essential for osteoclast development and bone marrow formation in colony-stimulating factor 1-deficient mice. (2005)
  • Author(s): S.Niida, T.Kondo, S.Hiratsuka, S.Hayashi, N.Amizuka, T.Noda, K.Ikeda, M.Shibuya.
  • Journal Title: Proc.Natl.Acad.Sci.USA 102(39) Pages: 14016-14021
  • Peer Reviewed
• [Journal Article] IP3 receptor types 2 and 3 mediate exocrine secretion underlying energy metabolism. (2005)
  • Author(s): A.Futatsugi, T.Nakamura, M.K.Yamada, E.Ebisui, K.Nakamura, K.Uchida, T.Kitaguchi, H.Takahashi-Iwanaga, T.Noda, J.Aruga, K.Mikoshiba.
  • Journal Title: Science 309(5744) Pages: 2232-2234
  • Peer Reviewed
• [Journal Article] Genetic analysis of Pten and Tsc2 functional interactions in the mouse reveals asymmetrical haploinsufficiency in tumor suppression. (2005)
  • Author(s): L.Ma, J.Teruya-Feldstein, N.Behrendt, Z.Chen, T.Noda, O.Hino, C.Cordon-Cardo, P.P.Pandolfi.
  • Journal Title: Genes Dev. 19(15) Pages: 1779-1786
  • Peer Reviewed
• [Journal Article] Targeted disruption of FSCN2 gene induces retinopathy in mice. (2005)
  • Author(s): S.Yokokura, Y.Wada, S.Nakai, H.Sato, R.Yao, H.Yamanaka, S.Ito, Y.Sagara, M.Takahashi, Y.Nakamura, M.Tamai, T.Noda.
  • Journal Title: Invest.Ophthalmol.Vis.Sci. 46(8) Pages: 2905-2915
  • Peer Reviewed
• [Journal Article] PKC λ regulates glucose-induced insulin secretion through modulation of gene expression in pancreatic beta cells. (2005)
  • Author(s): N.Hashimoto, Y.Kido, T.Uchida, T.Matsuda, K.Suzuki, H.Inoue, M.Matsumoto, W.Ogawa, S.Maeda, H.Fujihara, Y.Ueta, Y.Uchiyama, K.Akimoto, S.Ohno, T.Noda, M.Kasuga.
  • Journal Title: J.Clin.Invest. 115(1) Pages: 138-145
  • Peer Reviewed
• [Journal Article] Achlorhydria by ezrin knockdown : defects in the formation/expansion of apical canaliculi in gastric parietal cells. (2005)
  • Author(s): A.Tamura, S.Kikuchi, M.Hata, T.Katsuno, T.Matsui, H.Hayashi, Y.Suzuki, T.Noda, S.Tsukita, S.Tsukita.
  • Journal Title: J.Cell Biol. 169(1) Pages: 21-28
  • Peer Reviewed