| Project/Area Number |
20590590
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory medicine
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| Research Institution | Hyogo Medical University |
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Principal Investigator |
TAMAOKI Tomoko (HASHIMOTO Tomoko) 兵庫医科大学, 医学部, 教授 (10172868)
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| Co-Investigator(Kenkyū-buntansha) |
TSUJIMURA Toru 兵庫医科大学, 医学部, 教授 (20227408)
NAKANO Takashi 兵庫医科大学, 医学部, 教授 (10155781)
FUKUOKA Kazuya 兵庫医科大学, 医学部, 准教授 (80305721)
MORINAGA Tomonori 兵庫医科大学, 医学部, 助教 (10351818)
YOSHIKAWA Reigetsu 兵庫医科大学, 医学部, 助教 (90319864)
SAITO Yuko 兵庫医科大学, 医学部, 講師 (00254350)
YOSHIKAWA Yoshie 兵庫医科大学, 医学部, 助教 (10566673)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 悪性中皮腫 / 上皮型中皮腫 / ゲノム解析 / CDKN2A・2B / セマフォリン / VEGF / BAP1 / アレイCGH / 組織型特異性 / がん抑制遺伝子 / アスベスト暴露 / 遺伝子多型 / 遺伝子欠損 / p15 / アスベスト曝露 |
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| Research Abstract |
Malignant mesothelioma(MM) is an asbestos-related tumor. Array-based CGH was performed using MM primary-cultured cells established in Hyogo College of Medicine(HCM). In HCM-MM cell samples, frequent deletions were detected in 1p, 3p21, 4q, 9p21, 16p13 and 22q. We also used ATCC and Riken MM cells. All 21 MM cells showed homozygous deletions in the 9p21 region carrying the CDKN2A/p16 and CDKN2B/p15 genes. Homozygous or heterozygous deletions in the 22q region carrying the NF2 gene were detected in 80% of HCC-MM cells, and deletions in 3p21.1-21.31 in 50%. We focused on the 3p21 region because it was specific to the epithelioid type. Since 3p21.1 and 3p21.31 regions contain Semaphorin family genes that inhibit VEGF activity, we analyzed gene expression profiles and found that lower expression of several SEMA genes and higher expression of VEGFA in epithelioid MMs than in Met5a, a normal mesothelial cell line, suggesting that VEGFA biological activity may be higher in epithelioid MMs. Genome alterations of BAP1, located in 3p21.1, was detected in 15 of 16 epithelioid MMs ; biallelic deletions or monoallelic deletions with or without mutations. Immunostaining with anti-BAP1 antibody showed negative nuclear staining in most of epithelioid MMs. These BAP1 mutations and deletions were somatic, since no germinal mutations were detected. These results showed that BAP1 mutation plays a significant role in the pathogenesis of epithelioid MMs.
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