Role of diacylglycerol kinase delta in hepatocarcinogenesis

二酰甘油激酶δ在肝癌发生中的作用

• 批准号: 16591327
• 负责人: TAKETOMI Akinobu
• 金额: $ 2.18万
• 依托单位: KYUSHU UNIVERCITY
• 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-16591327/
• 关键词: diacylglycerol kinase; hepatocellular carcinoma; RT-PCR

Diacylglycerol kinases (DGKs), which catalyze phosphorylation of diacylglycerol (DAG) to phophatidic acid (PA), play an important role in the signal transduction downstream of phospholipid turnover. To characterize its role of neoplastic transformation, mouse embryonic fibroblasts derived from dgkd^<+/+> or dgkd^<+/-> were used. Dgkd^<+/-> cells were profoundly growth-inhibited versus dgkd^<+/+> cells. Dgkd^<+/-> cells showed a 50% decrease of inhibition of BrdU incorporation compared with dgkd^<+/+> cells. Foci formation of dgkd^<+/-> cells induced by H-Ras and SV40 T antigen was significantly suppressed when compared with that of dgkd^<+/+> cells. A neutralizing antibody to TGFα drastically reduced the number of foci of dgkd^<+/+> cells to the same level as that of dgkd^<+/-> cells. Semi-quantitative RT-PCR showed that DGKδ expression was upregulated in human hepatocellular carcinoma (HCC), in which a soluble form of TGFα was detected in large quantities in blood or urine, compared in non-cancerous liver tissues. Immunohistochemical study revealed that strong DGKδ-immunoreactivity was present at the leading edge of HCC, such as the site near portal vein or under the capsule of the tumor, in which high expression of TACE and TGFα was also detected.These observations provide a novel molecular mechanism of transformation and tumor progression via DGKδ action and a suitable therapeutic target in HCC.

二酰基甘油激酶（DGKS），将磷酸化甘油（DAG）催化为磷脂的转导磷脂的转化是肿瘤转化的作用^<+/+>或dgkd^<+/-与DGKD^<+/+>细胞的抑制作用相对于DGKD^<+/+>细胞，与DGKD^+/+>细胞相比，+/->细胞非常抑制了DGKD^+/+>细胞。 // +>细胞中和TGFα的抗体大大减少了一些LS的焦点。非癌性肝组织中的血液或尿液D量。 TGFα Was Also Detected.TheSESESESESESESESESESESESE S Rovide a novel molecular Mechanism of Transformation and Tumor Progression VIA DGKδ AND AND AND AND A SUITABLE THERAPEUTIC TARGET IN HCC.