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Approach to PTHrP gene therapy for oral cancer

Research Project

Project/Area Number 13470442
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionThe Nippon Dental University

Principal Investigator

TSUCHIMOCHI Makoto  The Nippon Dental Univ., school of dentistry Niigata, Professor, 新潟歯学部, 教授 (20095186)

Co-Investigator(Kenkyū-buntansha) HARADA Mikiko  The Nippon Dental Univ., school of dentistry Niigata, Lecturer, 新潟歯学部, 助手 (60339471)
KAWASE Tomoyuki  Niigata University, Graduate School Medical and Dental Sciences, Associate Professor, 大学院・医歯学総合研究科, 助教授 (90191999)
SAITO Eiichi  The Nippon Dental Univ., school of dentistry Niigata, Associate Professor, 新潟歯学部, 助教授 (40120662)
KAMETA Ayako  The Nippon Dental Univ., school of dentistry Niigata, Lecturer, 新潟歯学部, 助手 (00328866)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2002: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2001: ¥9,200,000 (Direct Cost: ¥9,200,000)
KeywordsPTHrP / cDNA Array / squamous cell carcinoma / oral cancer / differentiation / keratinocyte / cell cycle / hTERT / PTHrP遺伝子 / ケラチノサイト / ケラチン
Research Abstract

In previous clinical immunohistochemical studies, the authors found that parathyroid hormone-related protein (PTHrP) was expressed in oral squamous cell carcinoma in which the localization corresponded to regions of higher keratinization and tower grade of histologic malignancy. The purpose of this study was to examine the effect of PTHrP on proliferation and differentiation of oral squamous cells. We used a squamous carcinoma cell line, SCC-25, derived from tongue cancer, and an immortalized keratino cyte cell line, NDUSD-1, derived from human gingival tissue. PTHrP (1-34), (34-53), and (107-139) fragments were added to the culture medium. It has been reported that each of PTHrP fragments has different physiologic functions, such as regulation of smooth muscle tone, transepithelial calcium transport, and tissue and organ development, differentiation, and proliferation. For assessment of proliferation, we counted the number of cells. The ability of the fragments to affect differentiation was evaluated by using immunofluorescent staining with involucrin, cytokeratin (CK)10, CK14, CK5, CK6, and CK18. We also assessed intracellular cAMP concentration. No changes in cell number or immunofluorescence staining were evident in either cell line following stimulation with the fragments. The concentration of cAMP did not change in either cell line after adding the fragments. PTHrP fragment (1-34) did not increase CK expressions in NDUSD-1 in a cDNA microarray study. Although it has been reported that PTHrP affects differentiation of keratinocytes on antisense RNA study, we did not observe any influence of exogenously added PTHrP on cell differentiation and proliferation in the examined cell lines. The endogenous function of the fragments in oral squamous cells requires further study. Furthermore we examined in vitro effects of PTHrP by using cDNA array study. PTHrP could not reduce gene expression affecting cell proliferation.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Kameta A, Kang MK, et al.: "Absence of hamTERT gene expression is associated with promoter hypermethylation in immortal hamster buccal pouch epithelial cells."Int J Oncology. 22・6. 1351-1356 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kang MK, Kameta A, et al.: "Senescence-associated genes in normal human oral keratinocytes."Exp Cell Res. 287・2. 272-281 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kang MK, Kameta A, et al.: "Telomere shortening does not occur during postmaturational aging in situ in normal human oral fibroblasts."Mech Ageing Dev.. 124・8-9. 873-876 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kang MK, Kameta A, et al.: "Senescence occurs with hTERT repression and limited telomere shortening in human oral keratinocytes cultured with feeder cells."Journal of Cellular Physiology. published online(in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kameta A, Kang MK, Shin KH, Park NH: "Absence of hamTERT gene expression is associated with promoter hypermethylation in immortal hamster buccal pouch epithelial cells."Int J Oncology. 22-6. 1351-1356 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kang MK, Kameta A, Shin KH, Baluda MA, Kim HR, Park NH: "Senescence-associated genes in normal human oral keratinocytes."Exp Cell Res. 287-2. 272-281 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kang MK, Kameta A, Baluda MA, Park NH: "Telomere shortening does not occur during postmaturational aging in situ in normal human oral fibroblasts."Mech Ageing Dev. 124-(8-9). 873-876 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kang MK, Kameta A, Shin KH, Baluda MA, Park NH: "Senescence occurs with hTERT repression and limited telomere shortening in human oral keratinocytes cultured with feeder cells."Journal of Cellular Physiology (Accepted:7 July 2003,Published Online:25 Sep 2003). (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kameta A, Kang MK, et al.: "Absence of hamTERT gene expression is associated with promoter hypermethylation in immortal hamster buccal pouch epithelial cells."Int J Oncology. 22・6. 1351-1356 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kang MK, Kameta A, et al.: "Senescence-associated genes in normal human oral keratinocytes."Exp Cell Res. 287・2. 272-281 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kang MK, Kameta A, et al.: "Telomere shortening does not occur during postmaturational aging in situ in normal human oral fibroblasts."Mech Ageing Dev.. 124・8-9. 873-876 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kang MK, Kameta A, et al.: "Senescence occurs with hTERT repression and limited telomere shortening in human oral keratinocytes cultured with feeder cells."Journal of Cellular Physiology. published online(in press). (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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