Roles of P27/Skp2 pathway and identification of target genes on tumor malignancy of colon cancer

P27/Skp2通路及靶基因鉴定在结肠癌肿瘤恶性中的作用

• 批准号: 16591308
• 负责人: KAMIYA Kinji
• 金额: $ 2.3万
• 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 Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591308/
• 关键词: colon cancer; gastric cancer; Skp2; p27

Ubiquitin-proteasome pathway is a key system that controls cellular levels of number of proteins. This pathway is responsible not only for the degradation of short-lived proteins but also tumor suppressors, transcription factors and cell cycle proteins. Recently, it has been reported that degradation of Cdk inhibitory protein p27^<Kip1> is correlated with the prognosis of colon cancer. In this study, we investigated the molecular mechanisms of down-regulation of p27^<Kip1> and acquirement of tumor malignancy in the colon cancer.We established two cell lines, p27-hKO,p27 hetero-knockout HCT116 human colon cancer cell line and HCT-Skp2, transfected with Skp2 expression vector into HCT116 cells. We found the degradation of p27 protein in p27-hKO,HCT-Skp2 cells. Also we found that the invasive ability of p27-hKO,HCT-Skp2 cells is higher than HCT116 cells. Furthermore we applied comprehensive gene expression analysis between p27-hKO and HCT116 using microarray. As a result, function-unknown genes were overexpressed, and we demonstrated that the invasion ability of cancer cells was further increased by transfection of these genes.

泛素-蛋白酶体途径是控制细胞内蛋白质水平的关键系统。该途径不仅负责短寿命蛋白质的降解，还负责肿瘤抑制因子、转录因子和细胞周期蛋白的降解。最近，已经报道Cdk抑制蛋白p27 β的降解<Kip1>与结肠癌的预后相关。本研究建立了p27<Kip1>-hKO、p27异源敲除人结肠癌细胞系HCT 116和HCT-Skp 2两株细胞系，并将Skp 2表达载体转染HCT 116细胞，观察了Skp 2基因在结肠癌细胞系HCT 116中的表达。p27-hKO、HCT-Skp 2细胞中p27蛋白降解。p27-hKO、HCT-Skp 2细胞的侵袭能力高于HCT 116细胞。此外，我们使用微阵列在p27-hKO和HCT 116之间应用了全面的基因表达分析。结果，功能未知的基因被过度表达，我们证明了通过转染这些基因，癌细胞的侵袭能力进一步增加。

项目成果

Automated bedside measurement of penile blood flow using pulse-volume plethysmography

使用脉搏体积描记法自动床边测量阴茎血流量

• 发表时间: 2006
• 期刊: Surg Today 36
• 作者: Kikuchi;H. et al.;Unno N.et al.
• 通讯作者: Unno N.et al.

Immunohistochemical and genetic features of gastric and the metastatic liver GISTs, sequential analyses.

胃和转移性肝 GIST 的免疫组织化学和遗传特征，序贯分析。

• 发表时间: 2006
• 期刊: Cancer Sci. 97
• 作者: Nabetani;A.;Ishikawa;F.;Kikuchi.H.et al.
• 通讯作者: Kikuchi.H.et al.

Intestinal Behcet's disease with pyoderma gangrenosum : a case report

肠道白塞氏病伴坏疽性脓皮病：一例报告

• 发表时间: 2006
• 期刊: World J Gastroenterol 12
• 作者: Kikuchi;H. et al.;Unno N.et al.;Nakamura T. et al.
• 通讯作者: Nakamura T. et al.

Skp2-mediated degradation of p27 regulates progression into mitosis

• DOI: 10.1016/s1534-5807(04)00131-5
• 发表时间: 2004-05-01
• 期刊: DEVELOPMENTAL CELL
• 影响因子: 11.8
• 作者: Nakayama, K;Nagahama, H;Nakayama, KI
• 通讯作者: Nakayama, KI

Effect of MdmX on Mdm2-mediated downregulation of pRB

MdmX 对 Mdm2 介导的 pRB 下调的影响

• 发表时间: 2006
• 期刊: FEBS Letters 580
• 作者: Uchida;C.
• 通讯作者: C.