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THE MECHANISM OF DIFFERENTIATION IN SQUAMOUS CELL CARCINOMA CELLS AND INDUCTION OF APOPTOSIS IN HEAD AND NECK CARCINOMAS

Research Project

Project/Area Number 07457491
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionKochi Medical School

Principal Investigator

OSAKI Tokio  Kochi Medical School, Department of Oral Surgery, Professor, 医学部, 教授 (70031995)

Co-Investigator(Kenkyū-buntansha) UETA Eisaku  Kochi Medical School, Department of Oral Surgery, Research Associate, 医学部・附属病院, 助手 (10203431)
YAMAMOTO Tetsuya  Kochi Medical School, Department of Oral Surgery, Assistant Professor, 医学部・附属病院, 講師 (00200824)
YONEDA Kazunori  Kochi Medical School, Department of Oral Surgery, Associate Professor, 理学部, 助教授 (90182849)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordssquamous cell carcinoma cells / apoptosis / p53 / TGF-beta / 5-FU / gamma-rays / p21 / cyclin-dependent kinase / 扁平上皮癌
Research Abstract

We examined differentiation and apoptosis in both p53-wild type and p53-mutant type squamous cell carcinoma cell (SCC) lines and obtained the following results.
1. Differentiation was induced in all cell lines by vesnarinone (a differentiation inducer), 5-FU, TGF-beta and gamma-rays. p21 anti-sense inhibited vesnarinone- and TGF-beta-induced differentiation. Apoptosis was induced by peplomycin, 5-FU and gamma-rays although only weakly induced by TGF-beta and not induced by vesnarinone.
2. Accumulation of SCCs in the G1, S and G2/M phase was induced by vesnarinone, 5-FU and gamma-rays, respectively. However, the expression of cyclin D and E, Cdk2 and 4 was not changed by these reagents.
3. The p21-promoter activity was upregulated by TGF-beta in all cell lines but suppressed by other reagents. The p21 protein expression was increased by TGF-beta and vesnarinone (vesnarinone possessed a p21-mRNA-stabilizing activity) but 5-FU, peplomycin and gamma-rays suppressed the expression of p21.
4. By combinations of IL-2-induced cytotoxic lymphocytes and gamma-rays, 5-FU or others, apoptosis was more strongly induced.
5. Mn-SOD activity was inversely correlated with the induction of apoptosis. SCCs which possessed low level Mn-SOD activities more strongly fell into apoptosis than those with high Mn-SOD activities. Mn-SOD was also inversely associated with decrease of the potential (psi) of mitochondrial membrane and cleavage of caspase-3 and PARP.
These results indicate that however vesnarinone and TGF-beta induced differentiation in a p21-dependent manner, gamma-rays and 5-FU induce differentiation and apoptosis in p53- and p21-independent manners accumulating SCCs in the cell phase specific for each inducer, that combinations of cytotoxic lymphocytes and anticaner agents are useful for induction of apoptosis and that suppression of Mn-SOD activity is beneficial to induction of apoptosis in SCCs.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] 米田和典: "扁平上皮癌細胞におけるTGF-βと放射線による細胞周期の制御" 口腔組織培養研究会誌. 5. 55-67 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tetsuya Yamamoto: "Combination adoptive immunotherapy with chemoradiotherapy in oral carcinomas" Internationaru Journal of Clinical Oncology. 1. 150-156 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Eisaku Ueta: "Induction of defferentiation in maxillary adenoid cystic carcinomas by adoptive immunotherapy in combination with chemoradiotherapy" Oral Oncolgy. 34. 105-111 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kazunori Yoneda: "p53- and p21-independent apoptosis of squamous cell carci-noma cells induced by 5-fluorouracil and radiation" Oral Oncology. 34. 529-537 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kazunori Yoneda: "Induction of cyclin-dependent kioase inhibitor p21 in vesnarinone-induced differentiation of squamous cell carcinoma cells" Cancer Letters. 133. 35-45 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yukihiro Tatemoto: "Expression of p53 and p21 protein in oral squamous cell carcinoma : correlation with lymph node metastasis and response to chemoradiotherapy" Pathology : Research and Practice. 194. 821-830 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kazunori Yoneda: "Regulation of the cell cycle by TGF-beta and radiation in squamous cell carcinoma cells" The Japanese Journal of Tissue Culture Society for Dental Research. 5. 55-67 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tetsuya Yamamoto: "Combination adoptive immuno-therapy with chemoradiotherapy in oral carcinomas" International Journal of Clinical Oncology. 1. 150-156 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Eisaku Ueta: "Induction of differentiation in maxillary adenoid cystic carcinomas by adoptive immunotherapy in combination with chemoradiotherapy" Oral Oncology. 34. 105-111 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kazunori Yoneda: "p53-and p21-independent apoptosis of squamous cell carcinoma cells induced by 5-fluorouracil and radiation" Oral Oncology. 34. 529-537 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kazunori Yoneda: "Induction of cyclin-dependent kinase inhibitor p21 in vesnarinone-induced differentiation of squamous cell carcinoma cells" Cancer Letters. 133. 35-45 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yukihiro Tatemoto: "Expression of p53 and p21 protein in oral squamous cell carcinoma : correlation with lymph node metastasis and response to chemoradiotherapy" Pathology Research and Practice. 194. 821-830 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 米田和典: "扁平上皮癌細胞におけるTGF-βと放射線による細胞周期の制御" 口腔組織培養研究会誌. 5・1. 55-67 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tetsuya Yamamoto: "Combination adoptive immunotherapy with chemoradiotherapy in oral carcinomas" International Journal of Clinical Oncology. 1・3. 150-156 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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