Identification of a novel tumor marker(s), based on the comprehensive analysis of genes expressed selectively in micometastais site.

基于对微转移位点选择性表达的基因的综合分析，鉴定新的肿瘤标志物。

• 批准号: 16390163
• 负责人: MUKAIDA Naofumi
• 金额: $ 9.41万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390163/
• 关键词: Pim-3; serine; threonine kinase; apoptosis; hepatocellular carcinoma (HCC); pancreatic cancer; colorectal cancer; liver metastasis; chemokine; CCL2; CCR1; CCL3; 肺転移; 腫瘍壊死因子; 血管内皮増殖因子; スレオニンキナーゼ

1)Aberrant expression of a proto-oncogene with serine/threonine kinase activity; Pim-3, in malignant lesions of endoderm-derived organs. We compared gene expression patterns in pre-malignant and malignant lesions in murine hepatocarinogenesis model, by using fluorescent differential display method. As a result, we observed that a proto-oncogene with serine/threonine kinase activity, Pim-3 was aberrantaly expressed in pre-malignant and malignant lesions, but not normal hepatic tissues. Similar observations were obtained also on human hepatocellular carcinoma (HCC) and normal liver tissues. Pim-3 was constitutively expressed in human HCC cell lines and the inhibition of Pim-3 expression by short interfering RNA induced the apoptosis of human HCC cell lines. Pim-3 was not detected in other endoderm-derived organs such as pancreas and colon, but its expression was enhanced in the pre-malignant lesions and malignant lesions of these organs. In both human pancreatic cancer and colorectal can … More cer cell lines, Pim-3 was constitutively expressed and a pro-apoptotic molecule, Bad was co-localized with Pim and was phosphorylated at 112-Ser, which represents its inactive form. The inhibition of Pim-3 expression by short interfering RNA reduced the phosphorylation of Bad at 112-Ser and the expression of an anti-apoptotic molecule, Bcl-XL and eventually enhanced the apoptosis. These observations suggest that aberrant expression of Pim-3 can contribute to carcinogenesis in endoderm-derived organs, including liver, pancreas, and colon, by inhibiting apoptosis and that Pim-3 can be a novel tumor marker to detect pre-malignant and malignant lesions of these organs.2)Roles of chemokines and hepatocarcinogenesis and liver metastasis We observed that a chemokine, CCL3 and its receptor, CCR1, can inhibit the carcinogenesis in the early phase of murine hepatocarcinogenesis induced by diethylnitrosamine administration but that the CCL3-CCR1 axis can promote carcinogenesis of the same hepatocarcinogenesis, by inducing angiogenesis. We further demonstrated that another chemokine, CCL2 and its receptor, CCR2, can promote liver metastasis by activating hepatic stellate cells (Ito cells) and eventually accelerating neovascularization. Less

1）具有丝氨酸/苏氨酸激酶活性的原始癌基因的异常表达； PIM-3，在内胚衍生的器官的恶性病变中。我们使用荧光差分显示方法比较了鼠肝癌发生模型中恶性病变和恶性病变中的基因表达模式。结果，我们观察到具有丝氨酸/苏氨酸激酶活性的原始癌基因在恶性病变和恶性病变中表达了PIM-3，但不是正常的肝肝组织。也对人肝细胞癌（HCC）和正常肝组织也获得了类似的观察结果。 PIM-3在人HCC细胞系中始终表达，并且通过短干扰RNA诱导人HCC细胞系的凋亡，对PIM-3表达的抑制。在其他内胚层衍生的器官（例如胰腺和结肠）中未检测到PIM-3，但其表达在这些器官的恶性病变和恶性病变中得到了增强。在人类胰腺癌和结直肠癌中，均可表达PIM-3的更多CER细胞系，并且是促凋亡的分子，BAD与PIM共定位，并以112-Ser的磷酸化，代表其非活性形式。通过短相互作用的RNA抑制PIM-3表达可在112-SER和抗凋亡分子（BCL-XL）的表达中降低BAD的磷酸化，并最终增强了凋亡。这些观察结果表明，PIM-3的异常表达可以通过抑制凋亡，包括肝脏，胰腺和结肠在内的内胚层衍生的器官中的癌变，并且PIM-3可以是一种新型肿瘤标记，可以检测这些organs and oggens of ogenoke and ogenoke and Hepatis.2）Chebin.2）。观察到，趋化因子CCL3及其受体CCR1可以在二乙基硝基胺诱导的鼠肝癌发生早期抑制癌变，但CCL3-CCR1 Axis可以通过介绍的肝癌生成，通过涉及的肝癌生成，CCL3-CCR1轴可以促进相同的肝癌发生的癌变。我们进一步证明，另一种趋化因子CCL2及其受体CCR2可以通过激活肝星状细胞（ITO细胞）来促进肝转移，并最终加速新血管形成。较少的

项目成果

A proto-oncogene, Pim-3 with serine/threonine kinase activity, is aberrantly expressed in human colon cancer cells and can prevent Bad-mediated apoptosis.

原癌基因 Pim-3 具有丝氨酸/苏氨酸激酶活性，在人结肠癌细胞中异常表达，可以阻止 Bad 介导的细胞凋亡。

• 发表时间: 2007
• 期刊: Cancer Science 98(3)
• 作者: Popivanova BK;Li Y-Y;Zhen H;Omura K;Fujii C;Tsuneyama K;Mukaida N
• 通讯作者: Mukaida N

Essential involvement of IFN-γ in Clostridium difficile toxin A-induced enteritis

• DOI: 10.4049/jimmunol.172.5.3018
• 发表时间: 2004-03-01
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Ishida, Y;Maegawa, T;Mukaida, N
• 通讯作者: Mukaida, N

Chemokines In The Encyclopedia of Endocrine Diseases

内分泌疾病百科全书中的趋化因子

• 发表时间: 2004
• 作者: Mukaida;N
• 通讯作者: N

Cancer gene therapy using cytokine and chemokine genes.

使用细胞因子和趋化因子基因的癌症基因治疗。

• 发表时间: 2004
• 期刊: Annals of Cancer Research and Therapy 12
• 作者: Tomita Y;Yang X;Ishida Y;Nemoto-Sasaki Y;Kondo T;Oda M;Watanabe G;Chladakov GN;Fujii C;Mukaida N.;Mukaida N.
• 通讯作者: Mukaida N.

Interleukin-1β stimulates IL-8 expression through MAP kinase and ROS signaling in human gastric carcinoma cells

• DOI: 10.1038/sj.onc.1207867
• 发表时间: 2004-08-26
• 期刊: ONCOGENE
• 影响因子: 8
• 作者: Hwang, YS;Jeong, M;Jung, YD
• 通讯作者: Jung, YD