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Genomic diagnosis of ameloblastoma by high-resolution array comparative genomic hybridization and development of molecular target drug

Research Project

Project/Area Number 16K11711
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Surgical dentistry
Research InstitutionAichi Medical University

Principal Investigator

KAZAOKA YOSHIAKI  愛知医科大学, 医学部, 教授 (30233696)

Co-Investigator(Kenkyū-buntansha) 山田 陽一  愛知医科大学, 医学部, 准教授 (20345903)
太田 明伸  愛知医科大学, 医学部, 講師 (30438048)
大野 隆之  愛知医科大学, 医学部, 講師 (20434623)
シバスンダラン カルナン  愛知医科大学, 医学部, 講師 (30557096)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsameloblastoma / TLR / reactive oxygen species / エナメル上皮腫 / 実験腫瘍学 / ゲノム / マイクロアレイ / 腫瘍
Outline of Final Research Achievements

In this study, we performed comprehensive analysis using high-density array CGH and cDNA microarray technique with the tumor and their counterpart normal oral tissues from patients with ameloblastoma. As a result, aCGH analysis showed the minimal tumor-specific copy number gains and losses in all the patients. Next, analysis of gene expression in the established ameloblastoma cell line revealed high expression of certain Toll-like receptors (TLR). Knockdown of TLR gene expression decreased expression of inflammation-related genes and cancer-related genes, and further increased the activity of Caspase-3. On the other hand, stimulation with TLR ligands did not have an effect of promoting proliferation.

Academic Significance and Societal Importance of the Research Achievements

エナメル上皮腫は、侵襲性の高い歯原性上皮性腫瘍であり、その発生頻度は歯原性腫瘍全体のおよそ半数を占める。エナメル上皮腫におけるゲノム異常の解析は進んだが、増殖・生存・悪性化に関する分子機序には不明な点が多い。本研究では、エナメル上皮腫細胞の分子生物学的特徴を明らかにすることを目的として解析を行った。TLRは自然免疫に関する受容体分子であるが、近年の報告ではがんで発現増加が認められており、がん細胞の性状に与える影響が示唆されている。本研究において、エナメル上皮腫ではTLRの高発現が認められ、TLRを介したシグナルがエナメル上皮腫細胞の生存に関与する可能性が示唆された。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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