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2000 Fiscal Year Final Research Report Summary

The functions of DNA topoisomerase and genes regulated by DNA topology in differentiation.

Research Project

Project/Area Number 10671750
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionTOKYO DENTAL COLLEGE

Principal Investigator

KIZAKI Harutoshi  TOKYO DENTAL COLLEGE, DEPARTMENT OF BIOCHEMISTRY, PROFESSOR, 歯学部, 教授 (60051653)

Co-Investigator(Kenkyū-buntansha) OHTA Kazumasa  TOKYO DENTAL COLLEGE, DEPARTMENT OF BIOCHEMISTRY, ASSISTANT, 歯学部, 助手 (30307376)
TANIMOTO Yutaka  TOKYO DENTAL COLLEGE, DEPARTMENT OF BIOCHEMISTRY, ASSISTANT, 歯学部, 助手 (10276975)
Project Period (FY) 1998 – 2000
Keywordscellular differentiation / DNA topoisomerase / DNA topology / TIS / apoptosis / salivary gland tumor cells / PKCδ
Research Abstract

In cellular differentiation, various gene expression is regulated by altering DNA topology which is tightly modulated by DNA topoisomerase I and II.We identified two genes that were suppressed early in the incubation with topoisomerase inhibitors. One was highly homologous to hnRNPA1 which modulates splicing of selected transcripts or stabilizes mRNAs. The other was a novel gene, named as TIS, which spanned about 21 kb including 11 exons and was present as a single copy. It was expressed in most mouse tissues, but its function was unknown. Then, we analyzed the roles of topoisomerases and TIS gene in human salivary gland tumor cells (HSG) treated by differentiating agents such as topoisomerase inhibitor (etoposide), trans-retinoic acid (tRA) or dibutyryl cyclic AMP (bt2cAMP). Expression of topoisomerase I was reduced at the early state by tRA treatment but not by bt2cAMP.Expression of topoisomerase I was decreased by tRA, but at a lesser extent by bt2cAMP.The level of topoisomerase IIβ … More was low and was not altered. The results suggest that downregulation of topoisomerase IIα involves in arrest of cellular proliferation and initiation of differentiation through alterations in DNA topology. TIS gene expression was reduced at the early stage after the treatment of the agents, suggesting the involvement of TIS gene in differentiation. Recently, TIS has been known to play certain important role in neoplastic transformation, cytokine-induced T cell activation, neoplastic proliferation, and apoptosis.
Apoptosis is induced as terminal differentiation in various cells inculuding salivary gland acinar cells. Salivary gland acinar cells and HSG cells underwent apoptosis by a topoisomerase II inhibitor, etoposide. PKCδ is known to be cleaved by caspase-3 in apoptotic cells. We found a novel isoform of PKCδ which was insensitive to caspase-3 in mouse salivary glands. These findings suggest that a novel PKCδ isoform may have some important role in terminal differentiation of salivary gland cells.
Further studies are required to elucidate the role of topoisomerases and TIS gene using homogeneously differentiating cells as a model. Less

  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Onishi,Y.: "4-Piperidinopiperidine-resistant Iymphoma cells were resistant to dexamethazone-and A23187-induced apoptosis."Cancer Letters. 127. 147-153 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Onishi,Y.: "Cloning of the T/S gene suppressed by topoisomerase inhibitors."Gene. 215. 453-459 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 大西芳秋: "癌とアポトーシス概論"産婦人科の実際. 47・8. 1177-1182 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 谷本豊: "細胞死の制御機構と老化"Mebio. 15・11. 22-27 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 太田一正: "アポトーシスと疾病との関わり"病理と臨床. 16・12. 1524-1528 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanimoto,Y.: "Benzodiazepine receptor agonists mudulate thymocyte spoptosis through reduction of the mitochondrial transmembrane potenti"Jpn.J.Pharmacol.. 79. 177-183 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 木崎治俊: "核酸代謝とアポトーシス"痛風と核酸代謝. 23・2. 173-179 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Otsuka,W.: "Quantitative analysis of osteopontin gene expression using a real-time reverse transcription-polymerase chain reaction assay."J.Hard Tissue Biol.. 9・2. 47-55 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 橋本嘉幸: "新アポトーシスの分子医学"羊土社. 190 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 奥田克爾: "歯周病学最前線"日本歯科評論社. 354 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 日本老年医学会雑誌編集委員会: "今日の老年医学-臨床と基礎-"中外医学社. 249 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Onishi, Y.: "4-Piperidinopiperazine-resistant lymphoma cells were resistant to dexamethasone-and A23187-induced apoptosis."Cancer Letters. 127. 147-153 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Onishi, Y.: "Cloning of the TIS gene suppressed by topoisomerase inhibitors."Gene. 215. 453-459 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanimoto, Y.: "Benzodiazepine receptror agonists modulate thymocyte apptosis through reduction of mitochondrial transmembrane potential."Jpn J Pharmacol. 79. 177-183 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohtsuka, Y.: "Quantitative analysis of osteoontin gene expression with a real-time reverrse trabscription-polymerase chain reaction assay."J Hard Tissue Biol. 9. 47-55 (2000)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2002-03-26  

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