Prediction of minute prostatic cancer development by telomere length measured with tissue section FISH method.

• Project/Area Number: 17590325
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare
• Principal Investigator: IZUMIYAMA Naotaka Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare, Tokyo Metropolitan Institute of Gerontology, Research Assistants, 東京都老人総合研究所, 助手 (10158751)
• Co-Investigator(Kenkyū-buntansha): NAKAMURA Ken-ichi Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare, Tokyo Metropolitan Institute of Gerontology, Research Scientists, 東京都老人総合研究所, 研究員 (60159069) ; TAKUBO Kaiyo Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare, Tokyo Metropolitan Institute of Gerontology, Team Leaders, 東京都老人総合研究所, 研究部長 (00154956)
• Project Period (FY): 2005 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000); Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: Prostate / Telomere / Telomerase / FISH / Pathology / 核酸 / 癌 / ゲノム / 細胞・組織

Research Abstract

We invited Dr. Steven Poon from the BC Cancer Center, Canada, twice in 2005 and 2006, to work as a member of our research team. In collaboration with Dr. Poon, we devised a new software program, "Tissue Telo version 2", for measurement of telomere length using tissue sections. With this approach, and the use of fluorescence in situ hybridization (FISH) with a telomere-specific probe on tissue sections, we were able to measure telomere length in archival sections of prostatic tissue, and obtained the following data :
1.Difficulties with analysis of prostatic tissue
Prostatic tissue contains rough muscle and collagen fibers, which have very strong autofluorescence. This autofluorescence prevented us from measuring telomere length in epithelium and stroma. Although several methods for removing this autofluorescence were tried, sufficiently satisfactory fluorescence microscopy images could not be obtained. Thus it is more difficult to obtain good images using prostate than with gastrointestinal tissue.
2.Improvement of quantitative fluorescence in situ hybridization
We used centromere fluorescence intensity as an internal control, and expressed telomere length as the telomere/centromere intensity ratio (TCR). Moreover, we used TCR of cell block sections of TIG-1 to obtain more precise data. The normalized TCR was the TCR of a histologic section divided by the TCR of a section of TIG-1 from a cell block.
3.TCRs of carcinoma cells were 71-83% those of normal fibroblasts. On the basis of these different TCRs, it appeared feasible to distinguish cancer cells from fibroblasts.
4.TCRs of (luminal cells) were smaller than those of (basal cells) in the prostate gland. It is suggested that luminal and basal cells constitute different populations in the prostate.
5.TCRs of normal fibroblasts were different from those of cancer fibroblasts. It is suggested that these cell populations in the stroma are different.

Research Products

• [Journal Article] Telomere length variations in 6 mucosal cell types of gastric tissue observed using novel Q-FISH method (2007)
  • Author(s): Aida J, Izumiyama-Shimomura N, Nakamura K, Ishii A, Ishikawa N, Honma N, Kurabayashi R, Kammori M, Poon SSS, Arai T, Takubo K
  • Journal Title: Human Pathology (in press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Telemere length variations in 6 mucosal cell types of gastric tissue observed using novel Q-FISH method (2007)
  • Author(s): Aida J, Izumiama-Shimomura N, Nakamura K, Ishii A, Ishikawa N, Honma N, Kurabayashi R, Kammori M, Poon SSS, Arai T, Takubo K
  • Journal Title: Human Pathology (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Telmere lenght variations in 6 mucosal cell types of gastric tissue observed using novel Q-FISH method (2007)
  • Author(s): Aida J, Izumiyama-shimomura N, Nakamura K, Ishii A, ishikawa N, Honma N, Kurabayashi R, Kammmori M, Poon SSS, Arai T, Takubo K
  • Journal Title: Human Pathology (in press)
• [Journal Article] Specific subtelomere loss on chromosome der(11)t(3;11) (q23;q23)x2 in anaplastic thyroid cancer cell line OCUT-1 (2006)
  • Author(s): Kammori M, Onoda N, Nakamura K, Izumiyama N, Ogisawa K, Kurabayashi R, Ogawa T, Miura Y, Kaminishi M, Poon S, Takubo K
  • Journal Title: Int J Mol Med 18・1 Pages: 9-16
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Telomere shortening with aging in the human pancreas (2006)
  • Author(s): Ishii A, Nakamura K, Kishimoto H, Honma N, Aida J, Sawabe M, Arai T, Fujiwara M, Takeuchi F, Kato M, Oshimura M, Izumiyama N, Takubo K
  • Journal Title: Exp Gerontol 41・9 Pages: 882-886
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Specific subtelomere loss on chromosome der(11)t(3;11)(q23;q23)x2 in anaplastic thyroid cancer cell line OCUT-1 (2006)
  • Author(s): Kammori M, Onoda N, Nakamura K, Izumiyama N, Ogisawa K, Kurabayashi R, Ogawa T, Miura Y, Kaminishi M, Poon S, Takubo K
  • Journal Title: Int J Mol Med. 18-1 Pages: 9-16
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Telomere shortening with aging in the human pancreas (2006)
  • Author(s): Ishii A, Nakamura K, Kishimoto H, Honma N, Aida J, Sawabe M, Arai T, Fujiwara M, Takeuchi F, Kato M, Oshimura M, Izumiyama N, Takubo K
  • Journal Title: Exp Gerontol. 41・9 Pages: 882-886
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] speciffic subtelomere loss on chromosome der(11)t(3;11)(q23;q23)x2 in anaplastic thyroid cancer cell lime OCUT-1 (2006)
  • Author(s): Kammori M, Onoda N, Nakamura K, Izumiyama N, Ogisawa K, Kurabayashi R, Ogawa T, Miura Y, Kaminishi M, Poon S
  • Journal Title: Int J Mol Med 18・1 Pages: 9-16
• [Journal Article] Telomere shortening with aging in the human pancreas (2006)
  • Author(s): Ishii A, Nakamura K, Kishimoto H, Honma N, Aida J, Sawabe M, Arai T, Fujiwara M, Takeuchi F, Kato M, Oshimura M, Izumiyama N, Takaubo K
  • Journal Title: Exp Gerontol 41・9 Pages: 882-6
• [Journal Article] Specific subtelomere loss on chromosome der(11)t(3;11)(q23;q23)x2 in anaplastic thyroid cancer cell line QCUT-1. (2006)
  • Author(s): Kammori M, Onoda N, Nakamura K, Izumiyama N, Ogisawa K, Kurabayashi R, Ogawa T, Miura Y, Kaminishi M, Poon S, Takubo K.
  • Journal Title: Int J Mol Med in press
• [Journal Article] Expression of human telomerase reverse transcriptase gene and protein, and of estrogen and progesterone receptors, in breast tumors : Preliminary data from neo-adjuvant chemotherapy (2005)
  • Author(s): Kammori M, Izumiyama N, Hashimoto M, Nakamura K, Okano T, Kurabayashi R, Naoki H, Honma N, Ogawa T, Kaminishi M, Takubo K.
  • Journal Title: Int J Oncol 27 Pages: 1257-1263
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Expression of human telomerase reverse transcriptase gene and protein, and of estrogen and progesterone receptors, in breast tumors : Preliminary data from neo-adjuvant chemotherapy. (2005)
  • Author(s): Kammori M, Izumiyama N, Hashimoto M, Nakamura K, Okano T, Kurabayashi R, Naoki H, Honma N, Ogawa T, Kaminishi M, Takubo K.
  • Journal Title: Int J Oncol 27 Pages: 1257-1263
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] テロメア,テロメラーゼと発癌 (2005)
  • Author(s): 田久保海誉, 本間尚子, 仲村賢一, 泉山七生貴, 石井章雄, 新井冨生, 沢辺元司, 倉林理恵, 神森 眞
  • Journal Title: 細胞 37・4 Pages: 143-147
• [Book] 細胞 (37) 「テロメア、テロメラーぜと発癌」 (2005)
  • Author(s): 田久保海誉, 本間尚子, 仲村賢一, 泉山七生貴, 石井章雄
  • Total Pages: 5
  • Publisher: ニューサイエンス社
  • Description: 「研究成果報告書概要(和文)」より