A functional role of Par-4 in endometrial tumorigenesis

Par-4 在子宫内膜肿瘤发生中的功能作用

• 批准号: 20590352
• 负责人: SAEGUSA Makoto
• 金额: $ 3万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590352/
• 关键词: Par-4; 子宮内膜癌; アポトーシス; 細胞増殖; Par4; bc1-2; p21WAF1; 正常子宮内膜; 月経周期

Constitutively high levels of Par-4 expression were observed in epithelial cells through the menstrual cycle, in contrast to the transient up-regulation in stromal components in the menstrual stage, positively correlated with the phospho-p65 and apoptosis. Most ECs exhibited significant down-regulation, with positive links only to pp65 expression. Transfection of p65 led to transactivation of Par-4. Overexpression of Par-4 resulted in induction of not only apoptosis but also senescence, through changes in expression of bcl-2 and p21WAF1, respectively. Together, these findings suggest that a signaling cascade involving sequential activation of NF-_κB/p65 and Par-4 may participate in relatively early events of endometrial tumorigenesis, leading to modulation of cell kinetics including apoptosis and cell cycle progression.

PAR-4在月经周期的上皮细胞中呈高表达，与月经期间质成分的短暂上调相反，与磷酸化P65和细胞凋亡呈正相关。大多数内皮细胞表现出显著的下调，只与pp65的表达呈正相关。P65基因的转染导致PAR-4的反式激活。PAR-4的过表达不仅诱导细胞凋亡，而且通过改变bc1-2和p21WAF1的表达诱导细胞衰老。综上所述，这些发现表明，涉及NF-_κB/p65和PAR-4顺序激活的信号级联可能参与子宫内膜肿瘤发生的相对早期事件，导致细胞动力学的调节，包括细胞凋亡和细胞周期进展。

项目成果

アポトーシス関連遺伝子Par-4による子宮内膜細胞動態調節機構と発癌

凋亡相关基因Par-4对子宫内膜细胞动力学的调控机制及癌变机制

• 发表时间: 2010
• 作者: 三枝信;他
• 通讯作者: 他

Transcriptional regulation of pro-apoptotic Par-4 by NF-kB/p65 and its function in controlling cell kinetics during early events in endometrial tumorigenesis.

NF-kB/p65 对促凋亡 Par-4 的转录调节及其在子宫内膜肿瘤发生早期事件中控制细胞动力学的功能。

• 发表时间: 2010
• 期刊: J Pathol 221
• 作者: Saegusa M;Hashimura M;Kuwata T;Okayasu I.
• 通讯作者: Okayasu I.

Transcriptional regulation of pro-apoptotis Par4 by NF-κB/p65 and its function in controlling cell kinetics during early events in endometrial tumorigenesis

NF-κB/p65 对促凋亡 Par4 的转录调节及其在子宫内膜肿瘤发生早期事件中控制细胞动力学的功能

• 发表时间: 2010
• 期刊: Journal of Pathology
• 影响因子: 7.3
• 作者: Saegusa M;et al
• 通讯作者: et al