• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2001 Fiscal Year Final Research Report Summary

Mutational changes of EGFR mRNA in oral cancers and functions of a candidate tumor suppressor, doc-1

Research Project

Project/Area Number 10470384
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Morphological basic dentistry
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

MATSUO Kou  Faculty of Dentistry Kyushu University, Associate Professor, 大学院・歯学研究院, 助教授 (70238971)

Co-Investigator(Kenkyū-buntansha) KIYOSHIMA Tamotsu  Faculty of Dentistry Kyushu University, Research Associate, 大学院・歯学研究院, 助手 (20264054)
SAKAI Hidetaka  Faculty of Dentistry Kyushu University, Professor, 大学院・歯学研究院, 教授 (80136499)
Project Period (FY) 1998 – 2001
KeywordsEGFR / mutation / truncated EGFR / doc-1 / DNA replication / DNA polymerase α / primase / CDK2
Research Abstract

1) We examined the mutations in the coding region of the human Epidermal growth factor receptor (EGFR) gene in normal oral keratinocytes and oral squamous carcinoma cells. First, a tumor-associated silent mutation, which generates a unique BsrI restriction site, was detected at position 2073 only in malignant keratinocytes. The utility of the tumor-associated BsrI site for diagnostic applications is currently being explored. Second, we found that there is a truncated EGFR mRNA (〜1.5 kb) which lacks both transmembrane and kinase domains. The functional analyses of the truncated receptor is in progress.
2) We found that pDoc-1 (a protein form of a candidate tumor suppressor, doc-1 gene) associates with DNA polymerase α/primase (pol-α : primase), resulting in suppression of DNA synthesis. Using in vitro DNA replication assay revealed that pDoc-1 suppresses DNA replication, leveling at 〜50 %, by affecting the initiation step rather than elongation phase. The pol- α : primase binding domain in pDoc-1 is mapped to the amino-terminal six amino acids (MSYKPN). On the other hand, we demonstrated that pDoc-1 also associates with cyclin-dependent kinase 2(CDK2). More specifically, pDoc-1 associates with the monomeric nonphosphorylated form of CDK2. Amino acids 109-111 (TER) are necessary for pDoc-l's association with CDK2.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Ieyoshi Kobayashi et al.: "Immunohistochemical and ultrastructural study of a papillary cystadenocarcinoma arising from the sublingual gland.(Case Report)"J. Oral Pathol. Med. 28. 282-286 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Satoru Shintani et al.: "Intragenic mutation analysis of the human epidermal grwoth factor receptor (EGFR) gene in malignant human oral keratinocytes"Cancer Res.. 39. 4142-4147 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kou Matsuo et al.: "p12^<DOC-1>, a growth suppressor, associates with DNA polymerase α/primase"FASEB J. 14. 1318-1324 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kaori Shima et al.: "Incidence of human papillomavirus-16 and -18 infection and p53 mutation in patients with oral squamous cell carcinoma in Japan"Br. J. Oral Maxillofac. Surg.. 38. 445-450 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tamotsu Kiyoshima et al.: "Expression of p53 tumor suppressor gene in adenoid cystic and mucoepidermoid carcinomas of the salivary glands"Oral Oncol.. 37. 315-322 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shintani, S et al.: "p12^<DOC-1> is a novel CDK2-associated protein"Mol. Cell. Biol.. 20. 6300-6307 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ieyoshi Kobayashi et al.: "Immunohistochemical and ultrastructural study of a papillary cystadenocarcinoma arising from the sublingual gland"J. Oral Pathol. Med.. 28. 282-286 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Satoru Shintani et al.: "Intragenic mutation analysis of the human epidermal growth factor receptor (EGFR) gene in malignant human oral keratinocytes"Cancer Res.. 39. 4142-4147 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kou Matsuo et al.: "pl2^<DOC-1> , a growth suppressor, associates with DNA polymerase α/primase"FASEB J.. 14. 1318-1324 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shintani, S, et al.: "pl2^<DOC-1> is a novel CDK2-associated protein"Mol. Cell. Biol.. 20. 6300-6307 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kaori Shima et al.: "Incidence of human papillomavirus-16 and -18 infection and p53 mutation in patients with oral squamous cell carcinoma in Japan"Br. J. Oral Maxillofac Surg.. 38. 445-450 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tamotsu Kiyoshima et al.: "Expression of p53 tumor suppressor gene in adenoid cystic and mucoepidermoid carcinomas of the salivary glands"Oral Oncol.. 37. 315-322 (2001)

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

URL: 

Published: 2003-09-17  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi