Study on the abnormal centrosome regulation, leading to the chromosome instability in cancer

中心体调控异常导致癌症染色体不稳定的研究

• 批准号: 19790286
• 负责人: SHINMURA Kazuya
• 金额: $ 2.43万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19790286/
• 关键词: 中心体; 染色体不安定性; がん; p53; NORE1A; ベンゾピレン; 中心体過剰複製; hSgo1; 中心体サイクル; 非小細胞肺がん; EML4-ALK; がん抑制遺伝子; P53; B[a]PDE; hSgol; ヌクレオフオスミン; EML4; SUMO化

B[a]PDE, the ultimate carcinogenic metabolite of benzo[a]pyrene, contributes to neoplasia by inducing centrosome amplification and consequent chromosome destabilization as well as its mutagenic activity. hSgo1 is down-regulated in colorectal cancers and hSgo1 down-regulation leads to centrosome amplification and chromosome instability in colorectal cancer cells. The centrosomally localized p53 participates in the regulation of centrosome duplication in a manner independent of its transactivation function in addition to its transactivation-dependent regulation of centrosome duplication. NORE1A has activity that suppresses the centrosome amplification induced by hydroxyurea and NORE1A mRNA down-regulation is one of the common gene abnormalities in non-small cell lung carcinoma.

B [A] PDE是苯并[A] pyrene的最终致癌代谢产物，通过诱导中心体扩增和随之而来的染色体不稳定及其诱变活性来促进肿瘤。 HSGO1在结直肠癌中被下调，HSGO1下调导致结直肠癌细胞中的中心体扩增和染色体不稳定性。中心体定位的p53以与其反式激活功能无关的方式参与了中心体重复的调节，除了其反式激活依赖性依赖于中心体重复的调节。 Nore1a具有抑制羟基脲和Nore1a mRNA下调引起的中心体扩增的活性是非小细胞肺癌的常见基因异常。

项目成果

消化管癌におけるシュゴシン(hSgo1)の病理学的変化と染色体不安定性への関与.

Shugoshin (hSgo1) 参与胃肠癌的病理变化和染色体不稳定性。

• 发表时间: 2009
• 作者: 岩泉守哉;新村和也;森弘樹;山田英孝;北山康彦;伊熊睦博;椙村春彦
• 通讯作者: 椙村春彦

Identification and characterization of a novel germ line p53 mutation in familial gastric cancer in the Japanese population

日本人群家族性胃癌中新型种系 p53 突变的鉴定和表征

• 发表时间: 2007
• 期刊: Carcinogenesis 28
• 作者: Yamada H;et. al.
• 通讯作者: et. al.

Induction of centrosome amplification and chromosome instability in p53-deficient lung cancer cells exposed to benzo[a]pyrene diol epoxide (B[a]PDE)

• DOI: 10.1002/path.2422
• 发表时间: 2008-11-01
• 期刊: JOURNAL OF PATHOLOGY
• 影响因子: 7.3
• 作者: Shinmura, K.;Iwaizumi, M.;Sugimura, H.
• 通讯作者: Sugimura, H.

Human Sgol down-regulation leads to chromosomal instability in human colorectal cancer cells

人类 Sgol 下调导致人类结直肠癌细胞染色体不稳定

• 发表时间: 2009
• 期刊: Gut 58
• 作者: Iwaizumi M;et.al.
• 通讯作者: et.al.

Association between genetic polymorphisms of the base excision repair gene MUTYH and increased colorectal cancer risk in a Japanese population

• DOI: 10.1111/j.1349-7006.2007.00694.x
• 发表时间: 2008-02-01
• 期刊: CANCER SCIENCE
• 影响因子: 5.7
• 作者: Tao, Hong;Shinmura, Kazuya;Sugimura, Haruhiko
• 通讯作者: Sugimura, Haruhiko