2001 Fiscal Year Final Research Report Summary
Mutational changes of EGFR mRNA in oral cancers and functions of a candidate tumor suppressor, doc-1
| Project/Area Number |
10470384
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Morphological basic dentistry
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
MATSUO Kou Faculty of Dentistry Kyushu University, Associate Professor, 大学院・歯学研究院, 助教授 (70238971)
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| 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)
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| Project Period (FY) |
1998 – 2001
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| Keywords | EGFR / mutation / truncated EGFR / doc-1 / DNA replication / DNA polymerase α / primase / CDK2 |
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| 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.
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Research Products
(12 results)
