新規がん抑制遺伝子RB1CC1の生体内機能解析

• Project/Area Number: 15689008
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Shiga University of Medical Science
• Principal Investigator: 茶野 徳宏 滋賀医科大学, 医学部, 助教授 (40346028)
• Project Period (FY): 2003 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥25,480,000 (Direct Cost: ¥19,600,000、Indirect Cost: ¥5,880,000); Fiscal Year 2005: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000); Fiscal Year 2004: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000); Fiscal Year 2003: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
• Keywords: RB1CC1 / gene targeting / ES細胞 / RB1 / TSC / conditional / Cre-lox / Red / ET

Research Abstract

新規のがん抑制遺伝子であるRB1CC1の細胞生物学的な機序、生体内における働きを明らかにし、将来的には治療、創薬にも結びつけることを目標として研究を行った。
これまでに4種類のRb1cc1 targeting vectorsを構築し、組換えES細胞の樹立を図ってきた。各targeting vectorsにつき1,000個、計4,000個以上の薬剤耐性クローンのscreeningを行ってきたが、未だRb1cc1遺伝子相同組換えのおこったES細胞は樹立できていない。現在、version 5のconditional targeting vectorを用いて、組換えES細胞の樹立、conditional knock-out mouseの作成を継続進行中である。
一方で、CAG-loxP-neo-loxP-FlagRB1CC1導入によるtransgenic mouseを作成した。現在4系統のマウスラインを樹立できており、現在、主にMEFを使って解析を進めているが、本マウスはCre発現のvirusやマウスを使って各種臓器にconditionalなRB1CC1過剰発現を起こすことができる。今後、異所性のRB1CC1過剰発現が生体に起こす変化を解析してゆく。一つはマウス骨格筋や骨自身に起こるRB1CC1の過剰発現が栄養飢餓ストレス耐性であるか否か等について、また一つは本来RB1CC1発現の乏しい造血器系などでRB1CC1過剰発現が起こったときの病態を解析してゆきたい。

Research Products

• [Journal Article] Neuromuscular abundance of RB1CC1 contributes the non-proliferating enlarged cell phenotype through both RB1 maintenance and TSC1 degradation. (2006)
  • Author(s): Chano T, Saji M, et al.
  • Journal Title: Int J Mol Med 17(In press)
• [Journal Article] Imprinted DLK1 is a putative tumor suppressor gene and inactivated by epimutation at the region upstream of GTL2 in human renal cell carcinoma. (2006)
  • Author(s): Kawakami T, Chano T, et al.
  • Journal Title: Hum Mol Genet. 15(6) Pages: 821-830
• [Journal Article] HER2 protein in the serum and nipple discharge. (2005)
  • Author(s): Okabe H, Chano T, et al.
  • Journal Title: Nippon Rinsho 635(S8) Pages: 753-755
• [Journal Article] RB1CC1 is crucial for myoblast differentiation through RB1 regulation (2005)
  • Author(s): Watanabe R, Chano T, et al.
  • Journal Title: Virchows Arch 446(In press)
• [Journal Article] Expression and regulation of RB1CC1 in developing murine and human tissues (2004)
  • Author(s): Bamba N, Chano T, et al.
  • Journal Title: Int J Mol Med 14(4) Pages: 583-587
• [Journal Article] Differentially expressed genes in multidrug resistant variants of U-2 OS human osteosarcoma cells (2004)
  • Author(s): Chano T, et al.
  • Journal Title: Oncol Rep 11(6) Pages: 1257-1263
• [Publications] Teramoto K, Chano T, Ozaki Y, et al.: "Expression of RB1CC1, a novel tumor suppressor gene, is inversely correlated with the Ki-67 proliferation index in primary breast cancers"Cancer Therapy. 1. 103-107 (2003)
• [Publications] Kontani K, Chano T, Ozaki Y, et al.: "RB1CC1 suppresses cell cycle progression through RB1 expression in human neoplastic cells"Int J Mol Med. 12. 767-769 (2003)
• [Publications] Serra M, Maurici D, Benini S, Shen JN, Chano T, et al.: "Analysis of dihydrofolate reductase and reduced folate carrier gene status in relation to methotrexate resistance in osteosarcoma cells."Ann Oncol.. 15. 151-160 (2003)
• [Publications] Ushiyama T, Chano T, Inoue K, Matsusue Y.: "Cytokine production in the infrapatellar fat pad : another source of cytokines in knee synovial fluids108-12.2003."Ann Rheum Dis. 62. 108-112 (2003)
• [Publications] Mori K, Chano T, Ikeda T, Ikegawa S, Matsusue Y, Okabe H, Saeki Y.: "Decrease in serum nucleotide pyrophosphatase activity in ankylosing spondylitis."Rhuematology(Oxford). 42. 62-65 (2003)